Progesterone action in breast, uterine, and ovarian cancers

Abstract

Progesterone and progesterone receptors (PR) are essential for the development and cyclical regulation of hormone-responsive tissues including the breast and reproductive tract. Altered functions of PR isoforms contribute to the pathogenesis of tumors that arise in these tissues. In the breast, progesterone acts in concert with estrogen to promote proliferative and pro-survival gene programs. In sharp contrast, progesterone inhibits estrogen-driven growth in the uterus and protects the ovary from neoplastic transformation. Progesterone-dependent actions and associated biology in diverse tissues and tumors are mediated by two progesterone receptor isoforms, PR-A and PR-B. These isoforms are subject to altered transcriptional activity or expression levels, differential cross-talk with growth factor signaling pathways, and distinct post-translational modifications and cofactor binding partners. Herein, we summarize and discuss the recent literature focused on progesterone and PR isoform-specific actions in breast, uterine, and ovarian cancers. Understanding the complexity of context-dependent PR actions in these tissues is critical to developing new models that will allow us to advance our knowledge base with the goal of revealing novel and efficacious therapeutic regimens for these hormone-responsive diseases.

Nuclear Factor Erythroid 2-Related Factor 2 Deficiency Results in Amplification of the Liver Fat-Lowering Effect of Estrogen

“…During the steroid hormone treatment period, mice were continuously fed the HFD. Progesterone often exerts opposite effects to estrogen in many tissues (Diep et al, 2015). Hence, progesterone served as a potential negative control, whereas the combination of the two steroid hormones was used as a potential antagonistic control.…”

Progesterone receptor membrane component 1 promotes survival of human breast cancer cells and the growth of xenograft tumors

“…5,6 In contrast, an understanding of the actions of progestins in the development and progression of breast cancer is controversial. 7,8 In general, it is thought that progestins can both inhibit and stimulate proliferation of breast cancer cells. 9 The Women's Health Initiative Study firmly established that treatment with progestin in combination with estrogen (E2) for attenuating postmenopausal symptoms increases the risk of breast cancer, particularly TNBC.…”

Modifications to glucocorticoid and progesterone receptors alter cell fate in breast cancer

“…In the uterus, stromal PR (namely, PR-A) blocks the proliferative effects of epithelial ERα. The detailed actions of PR isoforms in the reproductive tract are the topic of a recent review (Diep et al 2015a).…”