Roma Sunder

ALT A schematic representation to describe the molecular mechanisms by which progesterone acts to curb cellular stress response and promote cell survival in breast cancer cells. Whole transcriptomic studies (represented by dotted lines) suggest that progesterone downregulates genes involved in the inflammatory response and TNF production while upregulating the central node ubiquitin gene UBC and N-myc downregulated gene 1, NDRG1, in primary breast tumors. Thus, the effects of progesterone are mediated through a negative regulation of inflammation. Biochemical and genetic studies (represented by solid lines) suggest that progesterone treatment of breast cancer cells in vitro increases the expression of a serum- and glucocorticoid-regulated kinase 1, SGK1, which upregulates NDRG1 via the AP-1 network genes, independent of the PR status of the cells. Progesterone also suppresses the expression of miR-29a and miR-101-1 that target the 3′-UTR of SGK1, reflecting a dual-regulatory model.