Prolactin receptor-integrin cross-talk mediated by SIRPα in breast cancer cells.

The hormone prolactin (PRL) contributes to the pathogenesis of breast cancer in part through its activation of Janus-activated kinase 2 (Jak2)/signal transducer and activator of transcription 5 (Stat5), a PRL receptor (PRLr)-associated pathway dependent on cross-talk signaling from integrins. It remains unclear, however, how this cross-talk is mediated. Following PRL stimulation, we show that a complex between the transmembrane glycoprotein signal regulatory protein-α (SIRPα) and the PRLr, β(1) integrin, and Jak2 in estrogen receptor-positive (ER(+)) and ER(-) breast cancer cells is formed.

Cyclophilin B as a co-regulator of prolactin-induced gene expression and function in breast cancer cells.

The effects of prolactin (PRL) during the pathogenesis of breast cancer are mediated in part though Stat5 activity enhanced by its interaction with its transcriptional inducer, the prolyl isomerase cyclophilin B (CypB). We have demonstrated that knockdown of CypB decreases cell growth, proliferation, and migration, and CypB expression is associated with malignant progression of breast cancer. In this study, we examined the effect of CypB knockdown on PRL signaling in breast cancer cells.

From bench to bedside: future potential for the translation of prolactin inhibitors as breast cancer therapeutics.

A role for prolactin (PRL) in the pathogenesis of breast cancer has been confirmed at the cellular level in vitro, with multiple transgenic and knockout models in vivo, and within sizable patient populations through epidemiologic analysis. It is the obvious "next step" that these findings are translated into meaningful therapies to block PRL/PRLr function in human breast cancer. Several broad categories of PRL/PRLr antagonists are discussed in their pre-clinical context, including inhibitors of endocrine PRL elaboration, mutant ligand antagonists, ligand chimeras, and inhibitors of PRL-induced signaling and transactivation.

Glucocorticoid induced expression of connective tissue growth factor contributes to lactogenic differentiation of mouse mammary epithelial cells.

The response of mammary epithelial cells to basement membrane and stroma induced signals contributes to the degree of differentiation in this tissue. The studies reported here indicate that connective tissue growth factor (CTGF) is highly elevated during lactogenic differentiation of the HC11 mouse mammary epithelial cell line. In addition, CTGF is expressed in the mouse mammary gland during pregnancy and lactation and it is expressed in primary mammary epithelial cell cultures established from pregnant mice.

EGF-induced activation of Akt results in mTOR-dependent p70S6 kinase phosphorylation and inhibition of HC11 cell lactogenic differentiation.

Background: HC11 mouse mammary epithelial cells differentiate in response to lactogenic hormone resulting in expression of milk proteins including beta-casein. Previous studies have shown that epidermal growth factor (EGF) blocks differentiation not only through activation of the Ras/Mek/Erk pathway but also implicated phosphatidylinositol-3-kinase (PI-3-kinase) signaling. The current study analyzes the mechanism of the PI-3-kinase pathway in an EGF-induced block of HC11 lactogenic differentiation.

Dominant negative Ras enhances lactogenic hormone-induced differentiation by blocking activation of the Raf-Mek-Erk signal transduction pathway.

Epidermal growth factor (EGF) and Ras mitogenic signal transduction pathways are frequently activated in breast carcinoma and inhibit mammary differentiation and apoptosis. HC11 mouse mammary epithelial cells, which differentiate and synthesize beta-casein following growth to confluency and stimulation with lactogenic hormones, were used to study EGF-dependent signaling during differentiation. Blocking Mek-Erk or phosphotidylinositol-3-kinase (PI-3 kinase) signaling with specific chemical inhibitors enhanced beta-casein promotor-driven luciferase activity.