Session: SAT 338-357-Steroid Hormone Actions
Poster Board SAT-343
Alejandro La Greca1, Daniel Soronellas2, Griselda Vallejo1, Guillermo Vicent2, Miguel Beato2, and Patricia Saragüeta1
1-Instituto de Biología y Medicina Experimental (IBYME-CONICET), Buenos Aires, Argentina
2-Centre de Regulació Genòmica, Barcelona, Spain.
It is established that progesterone acting via the progesterone receptor (PR) is a major determinant in the development and progression of breast cancer, as well as in endometrial pathologies. However, while PR-mediated crosstalk with other signalling pathways and its role in gene regulation are well described in breast cancer cells, PR signal transduction pathways and gene regulation in endometrial carcinoma cells is not fully understood yet. To explore the role played by PR in this tissue specific response, we have used chromatin immunoprecipitation coupled with next generation sequencing (ChIP-Seq) to examine the in vivo DNA binding of PR in hormone deprived Ishikawa endometrial carcinoma cells as well as in cells exposed for 5 and 60 min to the synthetic progestin R5020, and have compared the results to tose obtained with T47D breast cancer cells (1). Whole-Genome ChIP-Seq analysis has identified a large number of PR binding sites in Ishikawa cells as well as in T47D breast cancer cells, both ER-positive and PR-positive human carcinoma cells. We identified differences between endometrial adenocarcinoma and breast cancer cells. While PR genomic binding was highly hormone-dependent in T47D cells, high levels of PR binding was found in the genome of Ishikawa cells already prior to hormone exposure. Progestin promotes PR recruitment near the genes for many transcriptional regulators and chromatin remodelers, such as Satb2, Stx18, Prdm10, Tnfaip8 and Ltbr among others, indicating a role of PR in endometrial gene regulation. Our studies have identified specific molecular components in a progestin PR-regulated gene network involved in the regulation of endometrial cell function. Tissue-specific and common patterns of genome-wide PR binding and gene regulation may determine the therapeutic effects of antiprogestins in uterine pathologies and breast cancer.
Nothing to Disclose: AL, DS, GV, GV, MB, PS
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