Cell-type specific PR gene regulation in endometrial cancer cells

CRISTOBAL FRESNO; JAVIER QUILEZ-OLIETE; INTI TARIFA-REISCHLE; ALEJANDRO LA GRECA; RODRIGO JARA; GABRIELA MERINO; NICOLÁS BELLORA; FRANCOIS LE DILY; GABRIELA MERINO; CRISTOBAL FRESNO; FRANCOIS LE DILY; JAVIER QUILEZ-OLIETE; INTI TARIFA-REISCHLE; ALEJANDRO LA GRECA; RODRIGO JARA; NICOLÁS BELLORA

Congreso; Reunión Conjunta de Sociedades de Biociencias.; 2017

Estrogen (E2) and Progesterone (Pg) and their specific receptors ER and PR respectively are major determinants in the development and progression of breast and endometrial malignancies. We have studied the cell specificity of E2 and synthetic progestin R5020 action in human Ishikawa endometrial cancer cell line and compared it to similar genomic regulations in human T47D breast cancer cell line. Both hormones regulate pathways linked to cell proliferation in the breast and endometrial cancer cells, through different gene networks and signaling pathways. Using ChIPseq, we identified ~1,400 PRbs and ~1,900 ERbs which are largely specific for Ishikawa and distal (>50kb) to TSS of hormone regulated genes. Long-range interactions in chromatin structured genome analyzed by HiC showed that Ishikawa and T47D cells exhibit different A (open) and B (closed) chromatin compartments, which correlates with different hormone receptor binding distribution and gene regulation as indicated in PGR and Alpp genes. Among Ishikawa specific sites, the most representative motives found in PRbs were PRE, SOX and PAX, whereas in ERbs they were ERE and PAX. PR and ER bind mostly to non-common sites that exhibit the corresponding consensus sequences, and are adjacent to Pax2 binding. Therefore, the endometrial specific hormone response results in part from specific chromatin compartments, unique receptor binding sites and selective TFs binding partners.