Stimulating the GPR30 estrogen receptor with a novel tamoxifen analogue activates SF-1 and promotes endometrial cell proliferation
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Abstract
Estrogens and selective estrogen receptor (ER) modulators such as tamoxifen are known to increase uterine cell proliferation. Mounting evidence suggests that estrogen signaling is mediated not only by ERα and ERβ nuclear receptors, but also by GPR30 (GPER), a seven transmembrane (7TM) receptor. Here, we report that primary human endometriotic H-38 cells express high levels of GPR30 with no detectable ERα or ERβ. Using a novel tamoxifen analogue, STX, which activates GPR30 but not ERs, significant stimulation of the phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) pathways was observed in H-38 cells and in Ishikawa endometrial cancer cells expressing GPR30; a similar effect was observed in JEG3 choriocarcinoma cells. STX treatment also increased cellular pools of phosphatidylinositol (3,4,5) triphosphate, a proposed ligand for the nuclear hormone receptor SF-1 (NR5A1). Consistent with these findings, STX, tamoxifen, and the phytoestrogen genistein were able to increase SF-1 transcription, promote Ishikawa cell proliferation, and induce the SF-1 target gene aromatase in a GPR30-dependent manner. Our findings suggest a novel signaling paradigm that is initiated by estrogen activation of the 7TM receptor GPR30, with signal transduction cascades (PI3K and MAPK) converging on nuclear hormone receptors (SF-1/LRH-1) to modulate their transcriptional output. We propose that this novel GPR30/SF-1 pathway increases local concentrations of estrogen, and together with classic ER signaling, mediate the proliferative effects of synthetic estrogens such as tamoxifen, in promoting endometriosis and endometrial cancers. [Cancer Res 2009;69(13):5415–23]
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1 retracted
Vivacqua, A., Bonofiglio, D., Albanito, L., Madeo, A., Rago, V., Carpino, A., Musti, A. M., Picard, D., Andò, S., & Maggiolini, M. (2006) · Molecular Pharmacology · doi:10.1124/mol.106.026344 · Cited by 280 · see citing works
RetractedA transmembrane intracellular estrogen receptor mediates rapid cell signaling
Revankar, C. M., Cimino, D. F., Sklar, L. A., Arterburn, J. B., & Prossnitz, E. R. (2005) · Science · doi:10.1126/science.1106943 · Cited by 2,302 · see citing works
A Comparison of Letrozole and Tamoxifen in Postmenopausal Women with Early Breast Cancer
The Breast International Group (BIG) 1-98 Collaborative Group (2005) · New England Journal of Medicine · doi:10.1056/nejmoa052258 · Cited by 1,581 · see citing works
Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase
Simoncini, T., Hafezi‐Moghadam, A., Brazil, D. P., Ley, K. F., Chin, W. W., & Liao, J. K. (2000) · Nature · doi:10.1038/35035131 · Cited by 1,437 · see citing works
Identity of an Estrogen Membrane Receptor Coupled to a G Protein in Human Breast Cancer Cells
Thomas, P., Pang, Y., Filardo, E. J., & Dong, J. (2004) · Endocrinology · doi:10.1210/en.2004-1064 · Cited by 1,410 · see citing works
Filardo, E. J., Quinn, J. A., Bland, K. I., & Frackelton, A. R. (2000) · Molecular Endocrinology · doi:10.1210/mend.14.10.0532 · Cited by 1,387 · see citing works
Filardo, E. J., Quinn, J. A., Frackelton, A. R., & Bland, K. I. (2002) · Molecular Endocrinology · doi:10.1210/mend.16.1.0758 · Cited by 907 · see citing works
Virtual and biomolecular screening converge on a selective agonist for GPR30
Bologa, C., Revankar, C. M., Young, S. M., Edwards, B. S., Arterburn, J. B., Kiselyov, A. S., Parker, M. A., Tkachenko, S. E., Savchuk, N., Sklar, L. A., et al. (2006) · Nature Chemical Biology · doi:10.1038/nchembio775 · Cited by 819 · see citing works
Burney, R. O., Talbi, S., Hamilton, A. E., Vo, K. C., Nyegaard, M., Nezhat, C. R., Lessey, B. A., & Giudice, L. C. (2007) · Endocrinology · doi:10.1210/en.2006-1692 · Cited by 735 · see citing works
Integration of the extranuclear and nuclear actions of estrogen
Levin, E. R. (2005) · Molecular Endocrinology · doi:10.1210/me.2004-0390 · Cited by 708 · see citing works
Thomas, P., & Dong, J. (2006) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2006.09.017 · Cited by 604 · see citing works
Dinulescu, D. M., Ince, T. A., Quade, B. J., Shafer, S. A., Crowley, D. G., & Jacks, T. (2004) · Nature Medicine · doi:10.1038/nm1173 · Cited by 601 · see citing works
Carmeci, C., Thompson, D. A., Ring, H. Z., Francke, U., & Weigel, R. J. (1997) · Genomics · doi:10.1006/geno.1997.4972 · Cited by 590 · see citing works
Estrogen Signaling through the Transmembrane G Protein–Coupled Receptor GPR30
Prossnitz, E. R., Arterburn, J. B., Smith, H. O., Oprea, T. I., Sklar, L. A., & Hathaway, H. J. (2008) · Annual Review of Physiology · doi:10.1146/annurev.physiol.70.113006.100518 · Cited by 590 · see citing works
Nature of Functional Estrogen Receptors at the Plasma Membrane
Pedram, A., Razandi, M., & Levin, E. R. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0525 · Cited by 523 · see citing works
Qiu, J., Bosch, M. A., Tobias, S. C., Grandy, D. K., Scanlan, T. S., Rønnekleiv, O. K., & Kelly, M. J. (2003) · Journal of Neuroscience · doi:10.1523/jneurosci.23-29-09529.2003 · Cited by 460 · see citing works
Self-citationSato, N., Tsunoda, H., Nishida, M., Morishita, Y., Takimoto, Y., Kubo, T., & Noguchi, M. (2000) · PubMed · Cited by 451 · see citing works
Filardo, E. J., Quinn, J. A., Pang, Y., Graeber, C. T., Shaw, S. K., Dong, J., & Thomas, P. (2007) · Endocrinology · doi:10.1210/en.2006-1605 · Cited by 450 · see citing works
Maggiolini, M., Vivacqua, A., Fasanella, G., Recchia, A. G., Sisci, D., Pezzi, V., Montanaro, D., Musti, A. M., Picard, D., & Andò, S. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403588200 · Cited by 448 · see citing works
Krylova, I. N., Sablin, E. P., Moore, J. M. R., Xu, R. X., Waitt, G. M., MacKay, J. A., JUZUMIENE, D. I., Bynum, J. M., Madauss, K. P., Montana, V. G., et al. (2005) · Cell · doi:10.1016/j.cell.2005.01.024 · Cited by 405 · see citing works
Self-citationAlbanito, L., Madeo, A., Lappano, R., Vivacqua, A., Rago, V., Carpino, A., Oprea, T. I., Prossnitz, E. R., Musti, A. M., Andò, S., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-06-2909 · Cited by 399 · see citing works
Phosphorylation of the Nuclear Receptor SF-1 Modulates Cofactor Recruitment
Hammer, G. D., Krylova, I., Zhang, Y., Darimont, B. D., Simpson, K., Weigel, N. L., & Ingraham, H. A. (1999) · Molecular Cell · doi:10.1016/s1097-2765(00)80480-3 · Cited by 375 · see citing works
Self-citationFilardo, E. J. (2002) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/s0960-0760(01)00190-x · Cited by 374 · see citing works
Filardo, E. J., Graeber, C. T., Quinn, J. A., Resnick, M. B., Giri, D. D., DeLellis, R. A., Steinhoff, M. M., & Sabo, E. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-06-0860 · Cited by 361 · see citing works
Vivacqua, A., Bonofiglio, D., Recchia, A., Musti, A., Picard, D., Andò, S., & Maggiolini, M. (2006) · Molecular Endocrinology · doi:10.1210/me.2005-0280 · Cited by 345 · see citing works
Selective Estrogen-Receptor Modulators and Antihormonal Resistance in Breast Cancer
Jordan, V. C., & O’Malley, B. W. (2007) · Journal of Clinical Oncology · doi:10.1200/jco.2007.11.3886 · Cited by 325 · see citing works
Lynch, J. P., Lala, D. S., Peluso, J. J., Luo, W., Parker, K. L., & White, B. A. (1993) · Molecular Endocrinology · doi:10.1210/mend.7.6.8395654 · Cited by 266 · see citing works
Harrington, W. R., Kim, S. H., Funk, C. C., Madak‐Erdogan, Z., Schiff, R., Katzenellenbogen, J. A., & Katzenellenbogen, B. S. (2005) · Molecular Endocrinology · doi:10.1210/me.2005-0186 · Cited by 246 · see citing works
Liver Receptor Homologue-1 (LRH-1) Regulates Expression of Aromatase in Preadipocytes
Clyne, C. D., Speed, C. J., Zhou, J., & Simpson, E. R. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m201117200 · Cited by 233 · see citing works
A G-Protein-Coupled Estrogen Receptor Is Involved in Hypothalamic Control of Energy Homeostasis
Qiu, J., Bosch, M. A., Tobias, S. C., Krust, A., Graham, S. M., Murphy, S. J., Korach, K. S., Chambon, P., Scanlan, T. S., Rønnekleiv, O. K., et al. (2006) · The Journal of Neuroscience · doi:10.1523/jneurosci.0327-06.2006 · Cited by 217 · see citing works
Self-citationZeitoun, K., Takayama, K., Michael, M. D., & Bulun, S. E. (1999) · Molecular Endocrinology · doi:10.1210/mend.13.2.0229 · Cited by 216 · see citing works
Self-citationGPR30: a novel indicator of poor survival for endometrial carcinoma
Smith, H. O., Leslie, K. K., Singh, M., Qualls, C., Revankar, C. M., Joste, N. E., & Prossnitz, E. R. (2007) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2007.01.004 · Cited by 214 · see citing works
Attar, E., Tokunaga, H., Imir, G., Yilmaz, M. B., Redwine, D., Putman, M., Gurates, B., Attar, R., Yaegashi, N., Hales, D. B., et al. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1180 · Cited by 207 · cited 1× · see citing works
“Indeed, profiling studies comparing human ectopic and eutopic endometrium confirm that SF-1 and estradiol biosynthesis are amplified in ectopic disease tissue (38, 39).”
Self-citationGPR30 Contributes to Estrogen-Induced Thymic Atrophy
Chunhe, C., Dehghani, B., Magrisso, I. J., Rick, E. A., Bonhomme, E., Cody, D. B., Elenich, L. A., Subramanian, S., Murphy, S. J., Kelly, M. J., et al. (2007) · Molecular Endocrinology · doi:10.1210/me.2007-0359 · Cited by 206 · see citing works
Tamoxifen: Catalyst for the change to targeted therapy
Jordan, V. C. (2007) · European Journal of Cancer · doi:10.1016/j.ejca.2007.11.002 · Cited by 202 · see citing works
Estrogen receptors outside the nucleus in breast cancer
Levin, E. R., & Pietras, R. J. (2007) · Breast Cancer Research and Treatment · doi:10.1007/s10549-007-9618-4 · Cited by 168 · see citing works
Borghese, B., Mondon, F., Noël, J., Fayt, I., Mignot, T.-M., Vaiman, D., & Chapron, C. (2008) · Molecular Endocrinology · doi:10.1210/me.2008-0322 · Cited by 150 · see citing works
Filardo, E. J., QUINN, J., & Sabo, E. (2008) · Steroids · doi:10.1016/j.steroids.2007.12.025 · Cited by 110 · see citing works
Nongenomic actions of low concentration estrogens and xenoestrogens on multiple tissues
Watson, C. S., Alyea, R. A., Jeng, Y., & Kochukov, M. Y. (2007) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2007.05.011 · Cited by 108 · see citing works
Biochemical characterization of peritoneal fluid in women during the menstrual cycle
KONINCKX, P. R., VERHOEVEN, G., VAN BAELEN, H., LISSENS, W. D., DE MOOR, P., & BROSENS, I. A. (1980) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-51-6-1239 · Cited by 101 · see citing works
Structure of SF-1 Bound by Different Phospholipids: Evidence for Regulatory Ligands
Sablin, E. P., Blind, R. D., Krylova, I. N., Ingraham, J. G., Cai, F., Williams, J. D., Fletterick, R. J., & Ingraham, H. A. (2008) · Molecular Endocrinology · doi:10.1210/me.2007-0508 · Cited by 86 · see citing works
Self-citationAhola, T. M., Manninen, T., Alkio, N., & Ylikomi, T. J. (2002) · Endocrinology · doi:10.1210/en.2001-211445 · Cited by 86 · see citing works
Orphan nuclear receptors adopted by crystallography
Ingraham, H. A., & Redinbo, M. R. (2005) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2005.10.009 · Cited by 80 · see citing works
Self-citationSaxena, D., Escamilla, R., LITTLE-IHRIG, L. L., & Zeleznik, A. J. (2006) · Endocrinology · doi:10.1210/en.2006-0108 · Cited by 74 · see citing works
Steroidogenic factor-1 is a sphingolipid binding protein
Urs, A. N., Dammer, E. B., Kelly, S. L., Wang, E. L., Merrill, A. H., & Sewer, M. B. (2006) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2006.12.016 · Cited by 70 · see citing works
Aromatase as a Therapeutic Target in Endometriosis
Bulun, S. E., Zeitoun, K. M., Takayama, K., Simpson, E. R., & Sasano, H. (2000) · Trends in Endocrinology and Metabolism · doi:10.1016/s1043-2760(99)00216-7 · Cited by 48 · see citing works
Self-citationBukulmez, O., Hardy, D., Carr, B. R., Auchus, R., Toloubeydokhti, T., Word, R., & Mendelson, C. R. (2008) · Journal of Clinical Endocrinology and Metabolism · doi:10.1210/jc.2008-0248 · Cited by 40 · see citing works
Synthesis and Biological Evaluation of SERMs with Potent Nongenomic Estrogenic Activity
Tobias, S. C., Qiu, J., Kelly, M. J., & Scanlan, T. S. (2006) · ChemMedChem · doi:10.1002/cmdc.200500098 · Cited by 38 · see citing works
Self-citationGligorov, J., Pritchard, K. I., & Goss, P. E. (2007) · The Breast · doi:10.1016/j.breast.2007.10.003 · Cited by 13 · see citing works
Untangling the estrogen receptor web
Weatherman, R. V. (2006) · Nature Chemical Biology · doi:10.1038/nchembio0406-175 · Cited by 7 · see citing works
Bukulmez, O., Hardy, D., Carr, B., Auchus, R., Toloubeydokhti, T., Word, R., & Mendelson, C. (2009) · Obstetrical & Gynecological Survey · doi:10.1097/01.ogx.0000345377.28368.a5 · Cited by 2 · see citing works
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The G-protein-coupled estrogen receptor GPER in health and disease
Prossnitz, E. R., & Barton, M. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.122 · Cited by 925 · see citing works
“In turn, these signaling pathways also activate other transcription factors, such as steroidogenic factor 1”
BackgroundEstrogen biology: New insights into GPER function and clinical opportunities
Prossnitz, E. R., & Barton, M. (2014) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2014.02.002 · Cited by 404 · see citing works
The unfolding stories of GPR30, a new membrane-bound estrogen receptor
Maggiolini, M., & Picard, D. (2010) · Journal of Endocrinology · doi:10.1677/joe-09-0242 · Cited by 360 · see citing works
Obesity, insulin resistance and diabetes: sex differences and role of oestrogen receptors
Meyer, M. R., Clegg, D. J., Prossnitz, E. R., & Barton, M. (2011) · Acta Physiologica · doi:10.1111/j.1748-1716.2010.02237.x · Cited by 331 · see citing works
Minireview: steroidogenic factor 1: its roles in differentiation, development, and disease
Schimmer, B. P., & White, P. C. (2010) · Molecular Endocrinology · doi:10.1210/me.2009-0519 · Cited by 268 · see citing works
Prossnitz, E. R., & Arterburn, J. B. (2015) · Pharmacological Reviews · doi:10.1124/pr.114.009712 · Cited by 263 · see citing works
Endometriosis and nuclear receptors
Yilmaz, B. D., & Bulun, S. E. (2019) · Human Reproduction Update · doi:10.1093/humupd/dmz005 · Cited by 243 · see citing works
Self-citationFollicular assembly: mechanisms of action
Pepling, M. E. (2011) · Reproduction · doi:10.1530/rep-11-0299 · Cited by 243 · see citing works
Ariazi, E. A., Brailoiu, E., Yerrum, S., Shupp, H. A., Slifker, M. J., Cunliffe, H. E., Black, M. A., Donato, A. L., Arterburn, J. B., Oprea, T. I., et al. (2010) · Cancer Research · doi:10.1158/0008-5472.can-09-3068 · Cited by 236 · see citing works
Estrogen Receptor Function: Impact on the Human Endometrium
Yu, K., Huang, Z., Xu, X.-L., Li, J., Fu, X., & Deng, S. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.827724 · Cited by 236 · see citing works
Autophagy in the physiological endometrium and cancer
Devis, L., Eritja, N., Davis, M. L., Matías‐Guiu, X., & Llobet‐Navàs, D. (2020) · Autophagy · doi:10.1080/15548627.2020.1752548 · Cited by 226 · see citing works
Steroidogenic factor-1 (SF-1, NR5A1) and human disease
Ferraz‐de‐Souza, B., Lin, L., & Achermann, J. C. (2010) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2010.11.006 · Cited by 191 · see citing works
Kuo, J., Hamid, N., Bondar, G., Prossnitz, E. R., & Micevych, P. E. (2010) · Journal of Neuroscience · doi:10.1523/jneurosci.1158-10.2010 · Cited by 174 · see citing works
Hung, S. W., Zhang, R., Tan, Z., Chung, J. P. W., Zhang, T., & Wang, C. C. (2021) · Medicinal Research Reviews · doi:10.1002/med.21802 · Cited by 171 · see citing works
G Protein-Coupled Estrogen Receptor-Selective Ligands Modulate Endometrial Tumor Growth
Petrie, W. K., Dennis, M. K., Hu, C., Dai, D. D., Arterburn, J. B., Smith, H. O., Hathaway, H. J., & Prossnitz, E. R. (2013) · Obstetrics and Gynecology International · doi:10.1155/2013/472720 · Cited by 166 · see citing works
Yu, T., Yang, G., Hou, Y., Tang, X., Wu, C., Wu, X.-A., Guo, L., Zhu, Q., Luo, H., Du, Y.-E., et al. (2016) · Oncogene · doi:10.1038/onc.2016.370 · Cited by 149 · see citing works
Estrogen receptor β ligands: Recent advances and biomedical applications
Minutolo, F., Macchia, M., Katzenellenbogen, B. S., & Katzenellenbogen, J. A. (2009) · Medicinal Research Reviews · doi:10.1002/med.20186 · Cited by 147 · see citing works
Lebesgue, D., Traub, M., Butte-Smith, M. D., Chen, C. H., Zukin, R. S., Kelly, M. J., & Etgen, A. M. (2010) · PLoS ONE · doi:10.1371/journal.pone.0008642 · Cited by 146 · see citing works
Ge, L.-C., Chen, Z.-J., Liu, H.-Y., Zhang, K.-S., Liu, H., Huang, H.-B., Zhang, G., Wong, C. K. C., Giesy, J. P., Du, J., et al. (2014) · Toxicology Letters · doi:10.1016/j.toxlet.2014.01.035 · Cited by 129 · see citing works
Autotaxin in the crosshairs: Taking aim at cancer and other inflammatory conditions
Benesch, M. G. K., Ko, Y. M., McMullen, T. P. W., & Brindley, D. N. (2014) · FEBS Letters · doi:10.1016/j.febslet.2014.02.009 · Cited by 125 · see citing works
Sandén, C., Broselid, S., Cornmark, L., Andersson, K. A., Daszkiewicz-Nilsson, J., Mårtensson, U. E. A., Olde, B., & Leeb-Lundberg, L. M. F. (2010) · Molecular Pharmacology · doi:10.1124/mol.110.069500 · Cited by 121 · see citing works
Krolick, K. N., Zhu, Q., & Shi, H. (2018) · Progress in molecular biology and translational science · doi:10.1016/bs.pmbts.2018.07.008 · Cited by 121 · see citing works
Research advances in endometriosis-related signaling pathways: A review
Zhang, M., Xu, T., Tong, D., Li, S., Yu, X., Liu, B., Jiang, L., & Liu, K. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114909 · Cited by 119 · see citing works
Feldman, R. D., & Limbird, L. E. (2016) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010716-104651 · Cited by 109 · see citing works
Estrogen biosynthesis and signaling in endometriosis
Huhtinen, K., Ståhle, M., Perheentupa, A., & Poutanen, M. (2012) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2011.08.022 · Cited by 107 · see citing works
G Protein-Coupled Estrogen Receptor (GPER) Expression in Normal and Abnormal Endometrium
Plante, B. J., Lessey, B. A., Taylor, R. N., Wang, W., Bagchi, M. K., Yuan, L., Scotchie, J. G., Fritz, M. A., & Young, S. L. (2012) · Reproductive Sciences · doi:10.1177/1933719111431000 · Cited by 107 · see citing works
Catalano, S., Giordano, C., Panza, S., Chemi, F., Bonofiglio, D., Lanzino, M., Rizza, P., Romeo, F., Fuqua, S. A. W., Maggiolini, M., et al. (2014) · Breast Cancer Research and Treatment · doi:10.1007/s10549-014-3017-4 · Cited by 97 · see citing works
The signaling phospholipid PIP 3 creates a new interaction surface on the nuclear receptor SF-1
Blind, R. D., Sablin, E. P., Kuchenbecker, K. M., Chiu, H., Deacon, A. M., Das, D., Fletterick, R. J., & Ingraham, H. A. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1416740111 · Cited by 96 · see citing works
Self-citationGPER-mediated proliferation and estradiol production in breast cancer-associated fibroblasts
Luo, H., Yang, G., Yu, T., Luo, S., Wu, C., Sun, Y., Liu, M., & Tu, G. (2014) · Endocrine Related Cancer · doi:10.1530/erc-13-0237 · Cited by 89 · see citing works
Hypoxia: The force of endometriosis
Wu, M., Hsiao, K., & Tsai, S. (2019) · Journal of Obstetrics and Gynaecology Research · doi:10.1111/jog.13900 · Cited by 88 · see citing works
Whitby, R. J., Stec, J., Blind, R. D., Dixon, S., Leesnitzer, L. M., Orband‐Miller, L. A., Williams, S. P., Willson, T. M., Xu, R. X., Zuercher, W. J., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm1014296 · Cited by 79 · see citing works
Self-citationMéndez-Luna, D., Martínez‐Archundia, M., Maroun, R. C., Ceballos, G. M., Fragoso-Vázquez, M. J., González‐Juárez, D. E., & Correa‐Basurto, J. (2015) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2014.994102 · Cited by 75 · see citing works
Hsu, I., Yeh, C.-R., Slavin, S. A., Miyamoto, H., Netto, G. J., Tsai, Y.-C., Muyan, M., Wu, X., Messing, E. M., Guancial, E. A., et al. (2014) · Oncotarget · doi:10.18632/oncotarget.1421 · Cited by 72 · see citing works
Role of oestrogen receptors in bladder cancer development
Hsu, I., Vitkus, S., Da, J., & Yeh, S. (2013) · Nature Reviews Urology · doi:10.1038/nrurol.2013.53 · Cited by 71 · see citing works
Lee, E.-S., Sidoryk‐Wȩgrzynowicz, M., Yin, Z., Webb, A., Son, D., & Aschner, M. (2012) · Glia · doi:10.1002/glia.22329 · Cited by 70 · see citing works
Pupo, M., Vivacqua, A., Perrotta, I. D., Pisano, A., Aquila, S., Abonante, S., Gasperi‐Campani, A., Pezzi, V., & Maggiolini, M. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2013.05.023 · Cited by 69 · see citing works
Roy, D., Morgan, M., Yoo, C., Deoraj, A., Roy, S., Yadav, V., Garoub, M. M., Assaggaf, H. M., & Doke, M. (2015) · International Journal of Molecular Sciences · doi:10.3390/ijms161025285 · Cited by 67 · see citing works
The Neurosteroid Progesterone Underlies Estrogen Positive Feedback of the LH Surge
Micevych, P., & Sinchak, K. (2011) · Frontiers in Endocrinology · doi:10.3389/fendo.2011.00090 · Cited by 64 · see citing works
Minireview: Steroidogenic Factor 1: Its Roles in Differentiation, Development, and Disease
Schimmer, B. P., & White, P. C. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.95.3.9994 · Cited by 67 · see citing works
The G protein-coupled estrogen receptor as a modulator of neoplastic transformation
Jacenik, D., Cygankiewicz, A. I., & Krajewska, W. M. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.04.011 · Cited by 65 · see citing works
Kolková, Z., Noskova, V., Ehinger, A., Hansson, S. R., & Casslén, B. G. (2010) · Molecular Human Reproduction · doi:10.1093/molehr/gaq043 · Cited by 64 · see citing works
Chuang, S., Chen, C., Chou, Y., Ho, M., & Chang, J. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21186490 · Cited by 63 · see citing works
Activation of GPR30 inhibits cardiac fibroblast proliferation
Wang, H., Zhao, Z., Lin, M., & Groban, L. (2015) · Molecular and Cellular Biochemistry · doi:10.1007/s11010-015-2405-3 · Cited by 60 · see citing works
Low-dose Bisphenol-A regulates inflammatory cytokines through GPR30 in mammary adipose cells
Cimmino, I., Oriente, F., D’Esposito, V., Liguoro, D., Liguoro, P., Ambrosio, M. R., Cabaro, S., D’Andrea, F., Bèguinot, F., Formisano, P., et al. (2019) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0265 · Cited by 61 · see citing works
The effect of tamoxifen and raloxifene on estrogen metabolism and endometrial cancer risk
Williams‐Brown, M. Y., Salih, S. M., Xu, X., Veenstra, T. D., SAEED, M. K., Theiler, S., Diaz‐Arrastia, C., & Salama, S. A. (2011) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2011.05.001 · Cited by 59 · see citing works
Structure of Liver Receptor Homolog-1 (NR5A2) with PIP3 hormone bound in the ligand binding pocket
Sablin, E. P., Blind, R. D., Uthayaruban, R., Chiu, H., Deacon, A. M., Das, D., Ingraham, H. A., & Fletterick, R. J. (2015) · Journal of Structural Biology · doi:10.1016/j.jsb.2015.09.012 · Cited by 56 · see citing works
Self-citationPossible role of phytoestrogens in breast cancer via GPER-1/GPR30 signaling
Molina, L., Bustamante, F. A., Bhoola, K. D., Figueroa, C. D., & Ehrenfeld, P. (2018) · Clinical Science · doi:10.1042/cs20180885 · Cited by 57 · see citing works
Bryant, D. N., & Dorsa, D. M. (2010) · Neuroscience · doi:10.1016/j.neuroscience.2010.08.019 · Cited by 54 · see citing works
Selective GPER activation decreases proliferation and activates apoptosis in tumor Leydig cells
Chimento, A., Casaburi, I., Bartucci, M., Patrizii, M., Dattilo, R., Avena, P., Andò, S., Pezzi, V., & Sirianni, R. (2013) · Cell Death and Disease · doi:10.1038/cddis.2013.275 · Cited by 54 · see citing works
Bianco, S., Brunelle, M., Jangal, M., Magnani, L., & Gévry, N. Y. (2014) · Cancer Research · doi:10.1158/0008-5472.can-13-2351 · Cited by 54 · see citing works
G Protein-Coupled Estrogen Receptor in Energy Homeostasis and Obesity Pathogenesis
Shi, H., Kumar, S. P. D. S., & Liu, X. (2013) · Progress in molecular biology and translational science · doi:10.1016/b978-0-12-386933-3.00006-6 · Cited by 54 · see citing works
Oliver, K., Enewold, L., Zhu, K., Conrads, T. P., Rose, G. S., Maxwell, G. L., & Farley, J. H. (2011) · Gynecologic Oncology · doi:10.1016/j.ygyno.2011.06.027 · Cited by 53 · see citing works
Antiproliferation Activity of a Small Molecule Repressor of Liver Receptor Homolog 1
Corzo, C. A., Mari, Y., Chang, M. R., Khan, T. M., Kuruvilla, D. S., Nuhant, P., Kumar, N., West, G. M., Duckett, D. R., Roush, W. R., et al. (2014) · Molecular Pharmacology · doi:10.1124/mol.114.095554 · Cited by 51 · see citing works
Qiao, C., Ye, W., Li, S., Wang, H., & Ding, X. (2018) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2018.01.014 · Cited by 50 · see citing works
Molecular Characterization of Membrane Steroid Receptors in Hormone-Sensitive Cancers
Masi, M., Racchi, M., Travelli, C., Corsini, E., & Buoso, E. (2021) · Cells · doi:10.3390/cells10112999 · Cited by 49 · see citing works
Ge, X., Guo, R., Qiao, Y., Zhang, Y., Lei, J., Wang, X., Li, L., & Hu, D. (2012) · International Journal of Gynecological Cancer · doi:10.1097/igc.0b013e31827912b8 · Cited by 49 · see citing works
Kolková, Z., Casslén, V., Hénic, E., Ahmadi, S., Ehinger, A., Jirström, K., & Casslén, B. G. (2012) · Journal of Ovarian Research · doi:10.1186/1757-2215-5-9 · Cited by 49 · see citing works
Li, Y., Birnbaumer, L., & Teng, C. T. (2010) · Molecular Endocrinology · doi:10.1210/me.2009-0148 · Cited by 47 · see citing works
IQGAP1 is a phosphoinositide effector and kinase scaffold
Choi, S., & Anderson, R. A. (2015) · Advances in Biological Regulation · doi:10.1016/j.jbior.2015.10.004 · Cited by 47 · see citing works
A common hypofunctional genetic variant of GPER is associated with increased blood pressure in women
Feldman, R. D., Gros, R., Ding, Q., Hussain, Y., Ban, M. R., McIntyre, A. D., & Hegele, R. A. (2014) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.12471 · Cited by 46 · see citing works
Tamoxifen activates Nrf2-dependent SQSTM1 transcription to promote endometrial hyperplasia
Feng, L., Li, J., Yang, L., Zhu, L., Huang, X., Zhang, S., Luo, L., Jiang, Z., Jiang, T., Xu, W., et al. (2017) · Theranostics · doi:10.7150/thno.19135 · Cited by 45 · see citing works
Samartzis, N., Samartzis, E. P., Noske, A., Fedier, A., Dedes, K. J., Caduff, R., Fink, D., & Imesch, P. (2012) · Reproductive Biology and Endocrinology · doi:10.1186/1477-7827-10-30 · Cited by 43 · see citing works
Liu, C., Liao, Y., Fan, S., Tang, H., Jiang, Z., Zhou, B., Xiong, J., Zhou, S., Zou, M., & Wang, J. (2015) · Medical Oncology · doi:10.1007/s12032-015-0558-2 · Cited by 43 · see citing works
Repression of mammary adipogenesis by genistein limits mammosphere formation of human MCF-7 cells
Montales, M. T. E., Rahal, O. M., Nakatani, H., Matsuda, T., & Simmen, R. C. M. (2013) · Journal of Endocrinology · doi:10.1530/joe-12-0520 · Cited by 43 · see citing works
Role of GPR30 in endometrial pathology after tamoxifen for breast cancer
Ignatov, T., Eggemann, H., Semczuk, A., Smith, B., Bischoff, J., Roessner, A., Costa, S. D., Kalinski, T., & Ignatov, A. (2010) · American Journal of Obstetrics and Gynecology · doi:10.1016/j.ajog.2010.07.034 · Cited by 41 · see citing works
Lei, B., Peng, W., Xu, G., Wu, M., Wen, Y. C., Xu, J., Yu, Z., & Wang, Y. (2016) · Chemosphere · doi:10.1016/j.chemosphere.2016.11.066 · Cited by 41 · see citing works
Pathological functions of hypoxia in endometriosis
Hsiao, K.-Y. (2015) · Frontiers in Bioscience · doi:10.2741/e736 · Cited by 61 · see citing works
Vascular effects of aldosterone: Sorting out the receptors and the ligands
Feldman, R. D., & Gros, R. (2013) · Clinical and Experimental Pharmacology and Physiology · doi:10.1111/1440-1681.12157 · Cited by 40 · see citing works
Tran, Q., Firkins, R., Giles, J. R., Francis, S., Matnishian, V., Tran, P. N., VerMeer, M., Jasurda, J. S., Burgard, M., & Gebert‐Oberle, B. (2016) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.697334 · Cited by 40 · see citing works
Hasan, M., Marzouk, M. A., Adhikari, S., Wright, T. D., Miller, B. P., Matossian, M. D., Elliott, S. G., Wright, M. K., Alzoubi, M. S., Collins‐Burow, B. M., et al. (2019) · Molecular Pharmacology · doi:10.1124/mol.119.116202 · Cited by 40 · see citing works
Feldman, R. D., & Gros, R. (2011) · British Journal of Pharmacology · doi:10.1111/j.1476-5381.2011.01366.x · Cited by 39 · see citing works
Kenealy, B. P., Keen, K. L., Rønnekleiv, O. K., & Terasawa, E. (2011) · Endocrinology · doi:10.1210/en.2011-0097 · Cited by 39 · see citing works
Neuroprotective action of acute estrogens: Animal models of brain ischemia and clinical implications
Inagaki, T., & Etgen, A. M. (2013) · Steroids · doi:10.1016/j.steroids.2012.12.015 · Cited by 39 · see citing works
Carnesecchi, J., Malbouyres, M., Mets, R. D. M. D., Balland, M., Beauchef, G., Vié, K., Chamot, C., Lionnet, C., Ruggiero, F., & Vanacker, J.-M. (2015) · PLoS ONE · doi:10.1371/journal.pone.0120672 · Cited by 38 · see citing works
Feldman, R. D., Ding, Q., Hussain, Y., Limbird, L. E., Pickering, J. G., & Gros, R. (2016) · The FASEB Journal · doi:10.1096/fj.15-275552 · Cited by 38 · see citing works
Filigheddu, N., Sampietro, S., Chianale, F., Porporato, P. E., Gaggianesi, M., Gregnanin, I., Rainero, E., Ferrara, M., Perego, B., Riboni, F., et al. (2011) · Cellular Signalling · doi:10.1016/j.cellsig.2011.07.009 · Cited by 38 · see citing works
Phospholipid regulation of the nuclear receptor superfamily
Crowder, M. K., Seacrist, C. D., & Blind, R. D. (2016) · Advances in Biological Regulation · doi:10.1016/j.jbior.2016.10.006 · Cited by 37 · see citing works
Self-citationLi, Y., Chen, Y., Zhu-xia, Z., Liu, X., Yang, L., Wan, L., Lei, T., & Wang, X. (2013) · Toxicology · doi:10.1016/j.tox.2013.04.012 · Cited by 36 · see citing works
Chen, J., Hu, R., Ge, H., Duanmu, W., Li, Y., XUE, X., HU, S., & Feng, H. (2015) · Molecular Medicine Reports · doi:10.3892/mmr.2015.3601 · Cited by 35 · see citing works
Girgert, R., Emons, G., & Gründker, C. (2014) · BMC Cancer · doi:10.1186/1471-2407-14-935 · Cited by 34 · see citing works
Méndez-Luna, D., Bello, M., & Correa‐Basurto, J. (2016) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2016.01.001 · Cited by 34 · see citing works
Tian, R., Wang, Z., Shi, Z., Dong, L., Wang, Y., Zhu, Y., Lin, W., Gui, Y., & Zheng, X. (2012) · Fertility and Sterility · doi:10.1016/j.fertnstert.2012.09.011 · Cited by 33 · see citing works
Zhang, L., Li, Y., Lan, L., Liu, R., Wu, Y., Qu, Q., & Wen, K. (2016) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2016.08.011 · Cited by 33 · see citing works
He, Y., Du, G., Cai, B., Yan, Q., Zhou, L., Chen, X., Lu, W., Yang, Y.-X., & Wan, X. (2012) · Journal of Cancer Research and Clinical Oncology · doi:10.1007/s00432-011-1133-7 · Cited by 33 · see citing works
Tang, L., Li, X., Zhu, S.-Y., Wan, Y.-K., Zhang, S.-K., Ma, J., Yang, Y., Chen, A., Luo, L., & Cao, L.-Y. (2025) · Environmental Science & Technology · doi:10.1021/acs.est.4c13961 · Cited by 32 · see citing works
Mori, T., Ito, F., Matsushima, H., Takaoka, O., Tanaka, Y., Koshiba, A., Kusuki, I., & Kitawaki, J. (2015) · Fertility and Sterility · doi:10.1016/j.fertnstert.2015.01.026 · Cited by 31 · see citing works
Signaling through non-membrane nuclear phosphoinositide binding proteins in human health and disease
Bryant, J. M., & Blind, R. D. (2018) · Journal of Lipid Research · doi:10.1194/jlr.r088518 · Cited by 27 · see citing works
Self-citationLiu, J., Shelkar, G. P., Zhao, F., Clausen, R. P., & Dravid, S. M. (2019) · Molecular Pharmacology · doi:10.1124/mol.119.116780 · Cited by 28 · see citing works
Neurosteroids, trigger of the LH surge
Kuo, J., & Micevych, P. E. (2012) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2012.01.008 · Cited by 28 · see citing works
Burnett, L. A., Light, M. M., Mehrotra, P., & Nowak, R. A. (2012) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2012-2098 · Cited by 27 · see citing works
GPER modulators: Opportunity Nox on the heels of a class Akt
Prossnitz, E. R. (2017) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2017.03.005 · Cited by 26 · see citing works
Gros, R., Hussain, Y., Chorazyczewski, J., Pickering, J. G., Ding, Q., & Feldman, R. D. (2016) · Hypertension · doi:10.1161/hypertensionaha.116.07859 · Cited by 25 · see citing works
Various types of adenomyosis and endometriosis: in search of optimal management
Guo, S. (2023) · Fertility and Sterility · doi:10.1016/j.fertnstert.2023.03.021 · Cited by 24 · see citing works
Phosphatidylinositolphosphate phosphatase activities and cancer
Rudge, S. A., & Wakelam, M. J. O. (2015) · Journal of Lipid Research · doi:10.1194/jlr.r059154 · Cited by 24 · see citing works
Wang, J., Yu, R., Han, Q.-Q., Huang, H., Wang, Y.-L., Li, H., Wang, H., Chen, X., Ma, S., & Yu, J. M. (2018) · Behavioural Brain Research · doi:10.1016/j.bbr.2018.07.017 · Cited by 24 · see citing works
G protein-coupled estrogen receptor 1 as a novel regulator of blood pressure
Gohar, E. Y. (2020) · American Journal of Physiology-Renal Physiology · doi:10.1152/ajprenal.00045.2020 · Cited by 24 · see citing works
Aiad, H. A. S., Abdelwahed, M. M., Asaad, N. Y., Tahmody, M. E., & Elhosary, E. (2014) · Apmis · doi:10.1111/apm.12241 · Cited by 22 · see citing works
Kampa, M., Pelekanou, V., Gallo, D., Notas, G., Troullinaki, M., Pediaditakis, I., Charalampopoulos, I., Jacquot, Y., Leclercq, G., & Castanas, E. (2011) · Journal of Cellular Biochemistry · doi:10.1002/jcb.23309 · Cited by 22 · see citing works
de Valdivia, E. G., Sandén, C., Kahn, R., Olde, B., & Leeb-Lundberg, L. M. F. (2019) · Bioscience Reports · doi:10.1042/bsr20182436 · Cited by 22 · see citing works
Bryant, J. M., Malabanan, M. M., Vanderloop, B. H., Nichols, C. M., Haratipour, Z., Poon, K. T., Sherrod, S. D., MCLEAN, J. A. J., & Blind, R. D. (2021) · Journal of Lipid Research · doi:10.1016/j.jlr.2021.100081 · Cited by 21 · see citing works
Self-citation
- Authors
- Lin, B. C., Suzawa, M., Blind, R. D., Tobias, S. C., Bulun, S. E., Scanlan, T. S., & Ingraham, H. A.
- Affiliations
- 1Pharmaceutical Chemistry and Departments of
- University of California, San Francisco (US)
- Northwestern University (US)
- Oregon Health & Science University (US)
- Venue
- Cancer Research
- Published
- 2009-07-01
- Volume
- 69
- Issue
- 13
- Pages
- 5415-5423
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC2756996
- OpenAlex
- W2103019385
- Cited by
- 157
- References
- 51
- Citations by year
- 2026: 4 · 2025: 7 · 2024: 3 · 2023: 9 · 2022: 8 · 2021: 5 · 2020: 8 · 2019: 11 · 2018: 5 · 2017: 2 · 2016: 13 · 2015: 18 · 2014: 15 · 2013: 11 · 2012: 11
- FWCI
- 7.56
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- University of California, San Francisco
- National Institute of General Medical Sciences
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK063592, R01DK072246)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Keywords
- GPR30, G protein-coupled estrogen receptor, tamoxifen analogues, SF-1, steroidogenic factor 1, endometrial proliferation, endometriosis, endometrial cancer, PI3K signaling, MAPK signaling, phosphatidylinositol 3,4,5-trisphosphate, aromatase, genistein, estrogen signaling, choriocarcinoma
- MeSH terms
- Animals, Breast Neoplasms, Cell Division, Choriocarcinoma, Endometriosis, Estrogens, Female, Humans, Luciferases, Pregnancy, Receptors, Estrogen, Uterine Neoplasms, Endometrial Neoplasms, Genes, Reporter, Mice, Knockout, Receptors, G-Protein-Coupled, Cell Line, Tumor, Mice, Steroidogenic Factor 1
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