Analysis of Progestin Effects on Hepatocyte Growth Factor Signaling Pathways in Relation to Proliferation and Alveolar Morphogenesis of Normal Mammary Epithelial Cells in Vitro
Annual summary rept. 25 Mar 2002-24 Mar 2003
MICHIGAN STATE UNIV EAST LANSING
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Progestin action in the normal adult mammary gland has a major role in the formation of the alveolar bud structure during development and pregnancy. We have determined that for P-induced proliferation and morphogenesis to occur, the presence of hepatocyte growth factor HGF is required. When added alone to mouse primary cultures from adult virgin mice, HGF induces proliferation and a ductal morphology. With the addition of P we observe increased proliferation and an alveolar-like morphogenesis similar to that seen in response to P in the in vivo gland. We have therefore proposed to study the effects of P on HGFc-met signaling in an in vitro, serum free, three dimensional primary culture system using mammary epithelial cells. During the first year of this proposal methods for western blotting against c-Met were adapted for use in our culture system. The levels of c-Met were examined in response to the proposed treatments by immunostaining, showing that it is unlikely that the effects of HGF and progestins are mediated through changes in receptor expression. The effect of HCF and progestin treatment was also examined in pubertal mouse mammary epithelial organoids and did not exhibit the synergistic effect of HGF and progestin seen in adult mammary epithelial organoids.
- Anatomy and Physiology
- Medicine and Medical Research