Session: SAT 292-325-Breast & Prostate Cancer
Poster Board SAT-296
Results: P and MPA regulated a similar number of genes in PE4 (AR=PR), and both progestins reversed expression of ~30% of ER regulated genes. This coincided with a significant decrease in PE4 tumor growth with E+P or E+MPA compared to E alone. By contrast, MPA regulated four times as many genes as P in PT15 (AR>PR), and reversed few E regulated genes. PT15 grew significantly larger with E+MPA but not E+P, compared to E alone. Notably, <1% of P and <5% of MPA regulated genes overlapped between the two tumors. P and MPA regulated genes from either PE4 or PT15 shared <5% overlap with P and MPA regulated genes mapped in PR-rich T47D breast cancer cell lines and tumors (PR>AR). We conclude from these data: 1) progestins regulate unique gene cohorts in individual breast tumors, 2) the balance of PR vs. AR expression in breast tumors dictates the transcriptional response to MPA, and 3) the tumor specific gene network regulated by progestins may dictate whether they synergize or antagonize E-dependent growth. These data underscore the complexity of progestin response in heterogeneous steroid receptor expressing breast tumors and explain why strategies to uniformly agonize or antagonize PR have not been successful; natural or synthetic ligands with a more targeted response may offer new endocrine treatment options for receptor positive breast cancers.
Nothing to Disclose: JAF, PH, RBR, KF, AE, BMJ, PK, CAS
*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm
See more of: Abstracts - Orals, Featured Poster Presentations, and Posters