Grant: Operating Grant

The growth and development of the mammary gland is a complex process that begins during embryogenesis and continues postnatally through puberty, pregnancy and lactation and finally involution. During lactation the mammary epithelial cells are growth arrested and functionally mature to produce milk. Multiple growth factors regulate the various stages of mammary gland development. The hormone prolactin (PRL) is critical for the induction and maintenance of differentiation of mammary epithelial cells during lactation. Furthermore, recent evidence generated in our lab has highlighted the role of PRL as a suppressor of breast cancer aggressive phenotype. The signaling pathways operating downstream of PRL to regulate mammary gland development are not fully elucidated. We have previously shown that the protein tyrosine phosphatase SHP-2 plays an important role in PRL signaling leading to activation of the Jak2/Stat5a pathway, a critical pathway implicated in mammary epithelial cell differentiation. The objective of this proposal is to characterize further the role of SHP-2 in mediating PRL functions in the mammary gland and also define its role in breast cancer. In this proposal we expect to identify new signaling networks operating downstream of PRL/SHP-2 with important implications for the normal growth and Differentiation of the mammary gland.