The DOI matches its Crossref record; 75 of the 80 references it cites were found in a registry or an index.
HER2/neu kinase-dependent modulation of androgen receptor function through effects on DNA binding and stability.
Open accessAbstract
Given the role of the EGFR/HER2 family of tyrosine kinases in breast cancer, we dissected the molecular basis of EGFR/HER2 kinase signaling in prostate cancer. Using the small molecule dual EGFR/HER2 inhibitor PKI-166, we show that the biologic effects of EGFR/HER-2 pathway inhibition are caused by reduced AR transcriptional activity. Additional genetic and pharmacologic experiments show that this modulation of AR function is mediated by the HER2/ERBB3 pathway, not by EGFR. This HER2/ERBB3 signal stabilizes AR protein levels and optimizes binding of AR to promoter/enhancer regions of androgen-regulated genes. Surprisingly, the downstream signaling pathway responsible for these effects appears to involve kinases other than Akt. These data suggest that the HER2/ERBB3 pathway is a critical target in hormone-refractory prostate cancer.
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“Akt has been shown to have both agonistic and antagonistic influence on AR activity, either through direct phosphorylation of the receptor or through the action of downstream effectors, in both the presence and absence of androgen (49 -51).”
From Minireview: Alternative Activation Pathways for the Androgen Receptor in Prostate Cancer (2011) · cites this paper as [50]
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Cites
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., & McGuire, W. L. (1987) · Science · doi:10.1126/science.3798106 · Cited by 11,760
Dignam, J. D., Lebovitz, R. M., & Roeder, R. G. (1983) · Nucleic Acids Research · doi:10.1093/nar/11.5.1475 · Cited by 11,262
Sequence and structure-based prediction of eukaryotic protein phosphorylation sites
Blom, N., Gammeltoft, S., & Brunak, S. (1999) · Journal of Molecular Biology · doi:10.1006/jmbi.1999.3310 · Cited by 3,212
The ErbB signaling network: receptor heterodimerization in development and cancer
Olayioye, M. A., Neve, R. M., Lane, H. A., & Hynes, N. E. (2000) · The EMBO Journal · doi:10.1093/emboj/19.13.3159 · Cited by 2,489
Molecular determinants of resistance to antiandrogen therapy
Chen, C. D., Welsbie, D. S., Tran, C., Baek, S. H., Chen, R., Vessella, R., Rosenfeld, M. G., & Sawyers, C. L. (2004) · Nature Medicine · doi:10.1038/nm972 · Cited by 2,278
Self-citationActivation of the estrogen receptor through phosphorylation by mitogen-activated protein kinase
Kato, S., Endoh, H., Masuhiro, Y., Kitamoto, T., Uchiyama, S., Sasaki, H., Masushige, S., Gotoh, Y., Nishida, E., Kawashima, H., et al. (1995) · Science · doi:10.1126/science.270.5241.1491 · Cited by 1,964
Phosphorylation-induced binding and transcriptional efficacy of nuclear factor CREB
Yamamoto, K. K., Gonzalez, G. A., Biggs, W., & Montminy, M. (1988) · Nature · doi:10.1038/334494a0 · Cited by 1,281
Craft, N., Shostak, Y., Carey, M., & Sawyers, C. L. (1999) · Nature Medicine · doi:10.1038/6495 · Cited by 980
Holbro, T., Beerli, R. R., Maurer, F., Koziczak, M., Barbas, C. F., & Hynes, N. E. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1537685100 · Cited by 952
Čulig, Z., Hobisch, A., Cronauer, M. V., Radmayr, C., Trapman, J., Hittmair, A., Bartsch, G., & Klocker, H. (1994) · PubMed · Cited by 938
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Items 301–343 of 343
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Hatziieremia, S., McCall, P., & Edwards, J. (2011) · InTech eBooks · doi:10.5772/26971
JSM Clinical Oncology and Research
Onishi, T., & Sasaki, T. (2014)
Hsu, F.-N., Yang, M.-S., Lin, E. C., Tseng, C.-F., & Lin, H. (2011)
Factor Analysis of Microarray Data
Xu, S. (2012) · Springer eBooks · doi:10.1007/978-0-387-70807-2_21
The Ron receptor tyrosine kinase in prostate cancer.
Thobe, M. N. (2010) · OhioLink ETD Center (Ohio Library and Information Network)
The Role of EGFR, HER 2-4, Heregulin and Downstream Signalling in Prostate Adenocarcinoma
Grimsley, S. J. S. (2008) · Enlighten: Theses (The University of Glasgow)
Amplification and Overexpression of ERBB2, uPA, TRPS1, EIF3S3 and MYC Genes in Prostate Cancer
Savinainen, K. (2006) · Tampere University Institutional Repository (Tampere University)
ANALYSIS OF ENDOTHELIN DURING ANDROGEN DEPRIVATION: IMPLICATIONS FOR PROSTATE CANCER PROGRESSION
D’Antonio, J. M. (2007) · D-Scholarship@Pitt (University of Pittsburgh)
Expanding the Role of EGFR Inhibitors in Prostate Cancer
Sridhar, S. S., & Moore, M. J. (2006) · Translational medicine series · doi:10.3109/9781420019858.013
Targeted Prostate Cancer Chemoprevention Trial with Tocotrienols
Stone, W., Palau, V. E., Campbell, S., & Krishnan, K. (2012) · CRC Press eBooks · doi:10.1201/b12502-9
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Solit, D. B., Scher, H. I., & Rosen, N. X. (2006) · Translational medicine series · doi:10.3109/9781420019858.016
Identification of new urine biomarkers for the detection of prostate cancer
Rigau, M. (2011) · TDX (Tesis Doctorals en Xarxa)
Wong, N. (2016) · MacSphere (McMaster University) · doi:10.71548/15872
Hsu, F.-C., Yang, Y., & Lin, H. (2009)
Discovery Of Piperlongumine Derivatives As Anti-Leukemic And Anti-Prostate Cancer Agents
Liao, Y. (2018) · Human Biology
Molecular Biology and Prostate Cancer
Shaw, G. L., & Neal, D. E. (2012) · Springer eBooks · doi:10.1007/978-1-4471-2864-9_2
Wang, C. (2011) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.12333956.13515054
Immunotherapy as a Precision Medicine Tool for the Treatment of Prostate Cancer
Adamaki, M., Vassilios, A., & undefined, Z. (2020) · Vide Leaf, Hyderabad eBooks · doi:10.37247/pacr.1.2020.39
Lugovskoy, A. A., Curley, M. D., Lahdenranta, J., Kalra, A. V., Czibere, A. G., MacBeath, G., & Schoeberl, B. (2015) · Springer eBooks · doi:10.1007/978-1-4614-6613-0_95-1
Bevan, C. L., & Constantin, T. A. (2021) · Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · doi:10.3410/f.738340952.793583202
Lugovskoy, A. A., Curley, M. D., Lahdenranta, J., Kalra, A. V., Czibere, A. G., MacBeath, G., & Schoeberl, B. (2017) · Springer eBooks · doi:10.1007/978-1-4419-0717-2_95
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Cinar, B., Benedetti, A. D., & Freeman, M. R. (2023) · doi:10.1158/0008-5472.c.6494625
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Zhang, Y., Linn, D. E., Liu, Z., Melamed, J., Tavora, F. R. F., Young, C. Y. F., Burger, A. M., & Hamburger, A. W. (2023) · doi:10.1158/1535-7163.c.6531030.v1
Chen, L., Siddiqui, S., Bose, S., Mooso, B. A., Asuncion, A., Bedolla, R. G., Vinall, R. L., Tepper, C. G., Gandour‐Edwards, R. F., Shi, X.-B., et al. (2023) · doi:10.1158/0008-5472.c.6500427
Wang, G., Haile, S., Comuzzi, B., Tien, A. H., Wang, J., Yong, T. M. K., Jelescu-Bodos, A. E., Blaszczyk, N., Vessella, R. L., Masri, B. A., et al. (2023) · doi:10.1158/0008-5472.c.6499368.v1
Chen, L., Mooso, B. A., Jathal, M. K., Madhav, A., Johnson, S. D., Spyk, E. N. V., Mikhailova, M., Ripoll, A. Z., Xue, L., Vinall, R. L., et al. (2023) · doi:10.1158/1078-0432.c.6518943
Chen, L., Mooso, B. A., Jathal, M. K., Madhav, A., Johnson, S. D., Spyk, E. N. V., Mikhailova, M., Ripoll, A. Z., Xue, L., Vinall, R. L., et al. (2023) · doi:10.1158/1078-0432.c.6518943.v1
Wang, G., Haile, S., Comuzzi, B., Tien, A. H., Wang, J., Yong, T. M. K., Jelescu-Bodos, A. E., Blaszczyk, N., Vessella, R. L., Masri, B. A., et al. (2023) · doi:10.1158/0008-5472.22379841.v1
Qin, H. R., Iliopoulos, D., Nakamura, T., Costinean, S., Volinia, S., Druck, T., Sun, J., Okumura, H., & Huebner, K. (2023) · doi:10.1158/1541-7786.c.6542880
Qin, H. R., Iliopoulos, D., Nakamura, T., Costinean, S., Volinia, S., Druck, T., Sun, J., Okumura, H., & Huebner, K. (2023) · doi:10.1158/1541-7786.c.6542880.v1
Vellky, J. E., Kirkpatrick, B. J., Gutgesell, L. C., Morales, M., Brown, R. M., Wu, Y., Maienschein‐Cline, M., Notardonato, L. D., Weinfeld, M. S., Nguyen, R. H.-T., et al. (2024) · doi:10.1158/1078-0432.c.7181266.v1
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Staibano, S. (2013) · Springer eBooks · doi:10.1007/978-94-007-7149-9_8
Somatic Genetic Changes in Prostate Cancer
Helenius, M. A., Waltering, K. K., & Visakorpi, T. (2008) · Humana Press eBooks · doi:10.1007/978-1-60327-079-3_5
Gregory, C. W. (2009) · Annual Review of Biomedical Sciences · doi:10.5016/1806-8774.2009v11pt102
Ferrari, A. C., Chen, Y., Rodriguez, R., Hudes, G. R., Antonarakis, E. S., Hahn, N. M., Ma, H., Plimack, E. R., Mayer, T. M., Carthon, B. C., et al. (2026) · The Prostate · doi:10.1002/pros.70125
Bousset, L. (2019) · theses.fr (ABES) · doi:10.70675/45b0b676z18daz47a9zbb03zee607f300175
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Lee, Y. S., Zhao, J. L., Chryplewicz, A., Land, M., Sharma, R., Chan, J., Smith, P., Kottapalli, S., Fong, L. E., Chen, Z., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.07.30.741572
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Cheng, H. H., & Montgomery, B. (2014) · Current clinical urology · doi:10.1007/978-1-4939-1176-9_5
Metadata
- Authors
- Mellinghoff, I. K., Vivanco, I., Kwon, A., Tran, C., Wongvipat, J., & Sawyers, C. L.
- Affiliations
- University of California, Los Angeles (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Sawyers, Charles L.
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2004-11
- Volume
- 6
- Issue
- 5
- Pages
- 517-527
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2077863736
- Cited by
- 344
- References
- 80
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 6 · 2023: 15 · 2022: 6 · 2021: 10 · 2020: 10 · 2019: 6 · 2018: 10 · 2017: 15 · 2016: 16 · 2015: 17 · 2014: 17 · 2013: 20 · 2012: 23
- FWCI
- 19.11
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Health Sciences › Medicine › Oncology › HER2/EGFR in Cancer Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Estrogen and related hormone effects
- Keywords
- HER2/neu, androgen receptor, HER3, prostate cancer, castration-resistant prostate cancer, protein stability, DNA binding, transcriptional activity, Akt-independent signaling, tyrosine kinase inhibitors
- MeSH terms
- Animals, Chlorocebus aethiops, DNA, Neoplasm, Humans, Male, Prostatic Neoplasms, Proto-Oncogene Proteins, Pyrimidines, Pyrroles, Receptors, Androgen, Transfection, Tumor Cells, Cultured, Signal Transduction, Protein Serine-Threonine Kinases, Receptor, ErbB-2, Erb-b2 Receptor Tyrosine Kinases, COS Cells, RNA, Small Interfering, Proto-Oncogene Proteins c-akt, ErbB Receptors
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