Grant: Operating Grant

While it is known that breastfeeding is beneficial to the newborn, the contribution of breastfeeding/lactation to women's health is less acknowledged and has been largely ignored. Epidemiological studies have suggested that extended periods of breastfeeding/lactation produce protective effects to the mother against breast cancer independent of age, menopausal status or ethnic origin. It is also suggested that women in developed countries who in general have no or short lifetime duration of breastfeeding makes a major contribution to the high incidence of breast cancer in these countries. Therefore, it is essential to define at the molecular level how breastfeeding produce these protective effects against breast cancer. Unravelling the role of the lactation hormone prolactin (PRL) is the focus of our research program and this application. PRL is a primary factor required for mammary gland growth leading to induction and maintenance of lactation. We have made several important contributions in molecular cloning of the PRL receptor and characterizing downstream signaling mechanisms. Moreover, we have recently provided a new concept in PRL regulation of breast carcinogenesis. Most interestingly, our results indicate that PRL regulates plasticity of breast cancer cells leading to suppression in their invasive capacity (Cancer Research, 2006) and that mammary cells exposed to PRL become resistant to the proliferative effects of EGF, a factor implicated in mammary carcinogenesis (Molecular and Cellular Biology, 2009). In this proposal we plan to determine the role of PRL target genes in mammary epithelial differentiation and study their role in suppression of breast carcinogenesis. Such information will significantly accelerate progress into how breastfeeding/lactation may provide protective effects against breast cancer and will help in applying interventions to improve women's health and reduce breast cancer incidence and mortality.