Role of tyrosine kinase Jak2 in prolactin-induced differentiation and growth of mammary epithelial cells.

摘要: Genetic studies in mice have established a critical role for prolactin receptors and transcription factor Stat5 mammary gland differentiation. However, the enzymatic coupling between this process has not been established. In addition to Jak2, several other tyrosine kinases reportedly also are associated with may phosphorylate Stat5. Because Jak2 null die utero, we targeted an ex vivo model of prolactin-induced epithelial cell differentiation determine regulation growth. Two independent targeting strategies were used suppress immortalized HC11 mouse cells: 1) stable expression specific antisense construct 2) adenoviral delivery dominant-negative gene. We now demonstrate that is essential activation normal cells. Furthermore, suppression cells was constitutive oncoprotein Stat3 hyperproliferative phenotype characterized by increased mitotic rate, reduced apoptosis, contact inhibition. Collectively, our data suggest differentiation-inducing growth-inhibitory cells, observations shed new light on Jak2-Stat5 pathway breast cancer.