Regulation of Prolactin Receptor Levels and Activity in Breast Cancer

Abstract

From its traditional identity as a hormone involved in growth and differentiation of mammary epithelium and in lactation, to having a pertinent role in the development of mammary carcinoma, the peptide hormone/cytokine prolactin (PRL) has emerged as a versatile signaling molecule. There has been significant progress in our understanding of the fine working of PRL in the past several years. Notably, much effort has been concentrated on the mediator of PRL action, namely, the prolactin receptor (PRLr). The causal link between increased PRLr expression and breast cancer is being increasingly appreciated. Considering that the level of the receptor on the surface is a critical determinant of signaling output in response to PRL, the uncovering of regulatory elements that control receptor expression becomes important. The principle focus of this review is on the regulation of PRLr expression and activity in breast cancer with a brief overview of different isoforms of PRLr, their expression, signaling capabilities and the biological outcomes of PRL/PRLr signaling.

The Prolactin Receptor Transactivation Domain Is Associated with Steroid Hormone Receptor Expression and Malignant Progression of Breast Cancer

“…In previous studies, down-regulation of the PRLr resulted in slower cell growth in normal growth conditions. 21 Similarly, siRNA targeted against the PRLr inhibited cell proliferation ( Figure 3F). Taken as a whole, these results suggested that the PRLr, and specifically the Microarray values were analyzed in Partek Genomics Suite.…”

Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy

“…It has a three-domain organization: an extracellular ligand-binding domain, which confers specificity, a short transmembrane domain, and an ICD (Swaminathan et al 2008, Clevenger et al 2009). In addition to the most abundant 80 kDa long isoform, shorter variants that couple to different signaling pathways are detectable in breast cancer.…”

“…Whereas estrogens can bind to several classical (ERa and ERb) and nonclassical (G protein-coupled receptor 30, GPR30) receptors (Manavathi & Kumar 2006), there is only one receptor (PRLR) for PRL, albeit it exists in several isoforms which couple to different signaling pathways (Swaminathan et al 2008). Yet, there is crosstalk between the two hormones, with PRL increasing the expression and phosphorylation of ERa (Carver et al 2009), and E 2 inducing the transcription of both PRL (Duan et al 2008) and the PRLR (Swaminathan et al 2008). Such interactions can result in augmentation, or synergism, between the two hormones.…”

La prolactine et son fragment 16 kDa dans les tissus de mammifères

“…Les régulations de la quantité de récepteurs de la PRL et de leur activité de modulation des signalisations intracellulaires, ainsi que de la PRL endogène, pourraient être des facteurs de progression des tumeurs mammaires et prostatiques [2,33,34]. Des effets combinés des formes PRL 23 kDa et 16K, cette dernière pouvant avoir une activité antitumorale, ont été envisagés dans la croissance de tumeurs de la prostate [35].…”