Hagan, Christy R.;
Regan, Tarah;
Dressing, Gwen;
Lange, Carol
Abstract 2298: ck2-Dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B-isoform-specific target gene expression in breast cancer cells
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Medientyp:
E-Artikel
Titel:
Abstract 2298: ck2-Dependent phosphorylation of progesterone receptors (PR) on Ser81 regulates PR-B-isoform-specific target gene expression in breast cancer cells
Beteiligte:
Hagan, Christy R.;
Regan, Tarah;
Dressing, Gwen;
Lange, Carol
Erschienen:
American Association for Cancer Research (AACR), 2011
Erschienen in:
Cancer Research, 71 (2011) 8_Supplement, Seite 2298-2298
Beschreibung:
Abstract Progesterone receptors (PR) are critical mediators of mammary gland development and contribute to breast cancer progression. Progestin-induced rapid activation of cytoplasmic protein kinases leads to selective regulation of growth-promoting genes by phospho-PR species. Herein, we show that phosphorylation of PR Ser81 is ck2-dependent and progestin-regulated in intact cells, but also occurs in the absence of PR ligands, when cells enter the G1/S phase of the cell cycle. T47D breast cancer cells stably expressing a PR-B mutant that cannot be phosphorylated at Ser81 (S81A) formed fewer soft agar colonies. Regulation of selected genes by PR-B, but not PR-A, also required Ser81 phosphorylation for basal and/or progestin-regulated (BIRC3, HSD11β2, and HbEGF) expression. Additionally, wt PR-B, but not S81A mutant PR, was robustly recruited to a PRE-containing transcriptional enhancer region of BIRC3; abundant ck2 also associated with this region in cells expressing wt but not S81A PR. We conclude that phospho-Ser81 PR provides a platform for ck2 recruitment and regulation of selected PR-B target genes. Understanding how PR functions in the context of high kinase activities characteristic of breast cancer is critical to understanding the basis of tumor-specific changes in gene expression and will speed the development of highly selective treatments. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2298. doi:10.1158/1538-7445.AM2011-2298