Developmental role of the SNF1-related kinase Hunk in pregnancy-induced changes in the mammary gland

The steroid hormones 17 beta -estradiol and progesterone play a central rol e in the pathogenesis of breast cancer and regulate key phases of mammary g land development. This suggests that developmental regulatory molecules who se activity is influenced by ovarian hormones may also contribute to mammar y carcinogenesis, In a screen designed to identify protein kinases expresse d in the mammary gland, we previously identified a novel SNF1-related serin e/threonine kinase, Hunk (hormonally upregulated Neu-associated kinase), Du ring postnatal mammary development, Hunk mRNA expression is restricted to a subset of mammary epithelial cells and is temporally regulated with highes t levels of expression occurring during early pregnancy, In addition, treat ment of mice with 17 beta -estradiol and progesterone results in the rapid and synergistic upregulation of Hunk expression in a subset of mammary epit helial cells, suggesting that the expression of this kinase may be regulate d by ovarian hormones. Consistent with the tightly regulated pattern of Hun k expression during pregnancy, mammary glands from transgenic mice engineer ed to misexpress Hunk in the mammary epithelium manifest temporally distinc t defects in epithelial proliferation and differentiation during pregnancy, and-fail to undergo normal lobuloalveolar development. Together, these obs ervations suggest that Hunk may contribute to changes in the mammary gland that occur during pregnancy in response to ovarian hormones.