The DOI matches its Crossref record; 10 of the 10 references it cites were found in a registry or an index.
Increased Levels of COX-2 and Prostaglandin E2 Contribute to Elevated Aromatase Expression in Inflamed Breast Tissue of Obese Women
Open accessAbstract
Obesity is a risk factor for hormone receptor-positive breast cancer in postmenopausal women. Estrogen synthesis is catalyzed by aromatase, which is encoded by CYP19. We previously showed that aromatase expression and activity are increased in the breast tissue of overweight and obese women in the presence of characteristic inflammatory foci [crown-like structures of the breast (CLS-B)]. In preclinical studies, proinflammatory prostaglandin E2 (PGE2) is a determinant of aromatase expression. We provide evidence that cyclooxygenase (COX)-2–derived PGE2 stimulates the cyclic AMP (cAMP)→PKA signal transduction pathway that activates CYP19 transcription, resulting in increased aromatase expression and elevated progesterone receptor levels in breast tissues from overweight and obese women. We further demonstrate that a measure of in-breast inflammation (CLS-B index) is a better correlate of these biologic end points than body mass index. The obesity→inflammation→aromatase axis is likely to contribute to the increased risk of hormone receptor-positive breast cancer and the worse prognosis of obese patients with breast cancer. Significance: We show that obesity-associated inflammatory foci in the human breast are associated with elevated COX-2 levels and activation of the PGE2→cAMP→PKA signal transduction pathway resulting in increased aromatase expression. These findings help to explain the link among obesity, low-grade chronic inflammation, and breast cancer with important clinical implications. Cancer Discov; 2(4); 356–65. ©2012 AACR. Read the Commentary on this article by Wang and DuBois, p. 308 This article is highlighted in the In This Issue feature, p. 288
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Obesity is associated with macrophage accumulation in adipose tissue
Weisberg, S. P., McCann, D., Desai, M., Rosenbaum, M., Leibel, R. L., & Ferrante, A. W. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319246 · Cited by 10,041
Xu, H., Barnes, G. T., Yang, Q., Tan, G., Yang, D., Chou, C. J., Sole, J., Nichols, A., Ross, J. S., Tartaglia, L. A., et al. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200319451 · Cited by 6,760
Cinti, S., Mitchell, G., Barbatelli, G., Murano, I., Ceresi, E., Faloia, E., Wang, S., Fortier, M., Greenberg, A. S., & Obin, M. S. (2005) · Journal of Lipid Research · doi:10.1194/jlr.m500294-jlr200 · Cited by 2,529
Cancello, R., Henegar, C., Viguerie, N., Taleb, S., Poitou, C., Rouault, C., Coupaye, M., Pelloux, V., Hugol, D., Bouillot, J.-L., et al. (2005) · Diabetes · doi:10.2337/diabetes.54.8.2277 · Cited by 1,164
Nguyen, M. T. A., Favelyukis, S., Nguyen, A.-K., Reichart, D., Scott, P. A., Jenn, A., Liu-Bryan, R., Glass, C. K., Neels, J. G., & Olefsky, J. M. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706762200 · Cited by 1,035
Exemestane for Breast-Cancer Prevention in Postmenopausal Women
Goss, P. E., Ingle, J. N., Alés-Martínez, J. E., Cheung, A. M., Chlebowski, R. T., Wactawski-Wende, J., McTiernan, A., Robbins, J., Johnson, K. C., Martin, L. W., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103507 · Cited by 970
Murano, I., Barbatelli, G., Parisani, V., Latini, C., Muzzonigro, G., Castellucci, M., & Cinti, S. (2008) · Journal of Lipid Research · doi:10.1194/jlr.m800019-jlr200 · Cited by 726
Obesity and cancer: the role of dysfunctional adipose tissue
van Kruijsdijk, R. C. M., van der Wall, E., & Visseren, F. L. J. (2009) · Cancer Epidemiology, Biomarkers & Prevention · doi:10.1158/1055-9965.epi-09-0372 · Cited by 715
Bulun, S. E., Lin, Z., Imir, G., Amin, S., Demura, M., Yilmaz, B., Martin, R., Utsunomiya, H., Thung, S., Gurates, B., et al. (2005) · Pharmacological Reviews · doi:10.1124/pr.57.3.6 · Cited by 531
Sirianni, R., Chimento, A., De Luca, A., Zolea, F., Carpino, A., Rago, V., Maggiolini, M., Andò, S., & Pezzi, V. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.041020 · Cited by 41
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Iyengar, N. M., Gucalp, A., Dannenberg, A. J., & Hudis, C. A. (2016) · Journal of Clinical Oncology · doi:10.1200/jco.2016.67.4283 · Cited by 1,004
Self-citationBreast Cancer and Its Relationship with the Microbiota
Fernández, M. F., Reina-Pérez, I., Astorga, J. M., Rodríguez-Carrillo, A., Plaza-Díaz, J., & Fontana, L. (2018) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph15081747 · Cited by 350
Obesity and Breast Cancer: Role of Leptin
Sánchez-Jiménez, F., Pérez-Pérez, A., de la Cruz-Merino, L., & Sánchez-Margalet, V. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00596 · Cited by 268
Bhardwaj, P., Au, C. C., Benito-Martin, A., Ladumor, H., Oshchepkova, S., Moges, R., & Brown, K. A. (2019) · The Journal of Steroid Biochemistry and Molecular Biology · doi:10.1016/j.jsbmb.2019.03.002 · Cited by 233
Contribution of adipose tissue to development of cancer
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Metadata
- Authors
- Subbaramaiah, K., Morris, P. G., Zhou, X. K., Morrow, M., Du, B., Giri, D., Kopelovich, L., Hudis, C. A., & Dannenberg, A. J.
- Venue
- Cancer Discovery
- Published
- 2012-04-01
- Volume
- 2
- Issue
- 4
- Pages
- 356-365
- ISSN
- 2159-8274 (ISSN-L)
- 2159-8290
- OpenAlex
- W2171087521
- Cited by
- 244
- References
- 10
- FWCI
- 15.24
- Type
- journal article
- Language
- en
- Status
- Retracted
- Open access
- green
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- CoChat. (2026). Citation check: Increased Levels of COX-2 and Prostaglandin E2 Contribute to Elevated Aromatase Expression in Inflamed Breast Tissue of Obese Women. https://app.cochat.ai/papers/10.1158/2159-8290.cd-11-0241
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- Subbaramaiah, K., Morris, P. G., Zhou, X. K., Morrow, M., Du, B., Giri, D., Kopelovich, L., Hudis, C. A., & Dannenberg, A. J. (2012). Increased Levels of COX-2 and Prostaglandin E2 Contribute to Elevated Aromatase Expression in Inflamed Breast Tissue of Obese Women. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-11-0241
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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