Progesterone Receptors (PR) Mediate STAT Actions: PR and Prolactin Receptor Signaling Crosstalk in Breast Cancer Models

Publication date: Available online 23 April 2017 Source:The Journal of Steroid Biochemistry and Molecular Biology Author(s): Katherine A. Leehy, Thu H. Truong, Laura J. Mauro, Carol A. Lange Estrogen is the major mitogenic stimulus of mammary gland development during puberty wherein ER signaling acts to induce abundant PR expression. PR signaling, in contrast, is the primary driver of mammary epithelial cell proliferation in adulthood. The high circulating levels of progesterone during pregnancy signal through PR, inducing expression of the prolactin receptor (PRLR). Cooperation between PR and prolactin (PRL) signaling, via regulation of downstream components in the PRL signaling pathway including JAKs and STATs, facilitates the alveolar morphogenesis observed during pregnancy. Indeed, these pathways are fully integrated via activation of shared signaling pathways (i.e. JAKs, MAPKs) as well as by the convergence of PRs and STATs at target genes relevant to both mammary gland biology and breast cancer progression (i.e. proliferation, stem cell outgrowth, tissue cell type heterogeneity). Thus, rather than a single mediator such as ER, transcription factor cascades (ER > PR > STATs) are responsible for rapid proliferative and developmental programming in the normal mammary gland. It is not surprising that these same mediators typify uncontrolled proliferation in a majority of breast cancers, where ER and PR are most often co-expressed and may cooperate to dri...
Source: The Journal of Steroid Biochemistry and Molecular Biology - Category: Biochemistry Source Type: research