PROGESTERONE, IN ADDITION TO ESTROGEN, INDUCES CYCLIN D1 EXPRESSION IN THE MURINE MAMMARY EPITHELIAL-CELL, IN-VIVO

Previous investigations, in vitro, have demonstrated that progestins c an induce the transcription of the cell cycle regulator, cyclin D1, th ereby suggesting that cyclin D1 may mediate, at the molecular level, t he proposed mitogenic effects of progesterone during mammary epithelia l cell proliferation. To extend these initial studies into an in viva context, comparative cyclin D1 Northern and immunohistochemical analys es were performed on mammary gland tissue isolated from wild type (WT) females as well as from the recently reported progesterone receptor k nockout (PRKO) mouse model. Northern analysis revealed that estrogen i nduced cyclin D1 expression, 5- to 7-fold over control levels, both in the WT and PRKO female. Immunohistochemistry demonstrated that, for b oth test groups, the number of mammary epithelial cells expressing cyc lin D1 increased significantly as compared with control values, in res ponse to estrogen. In the case of estrogen plus progesterone treatment , Northern analysis revealed that, in the WT gland, cyclin D1 transcri ption increased approximately 3-fold over estrogen induced levels, an increase that was paralleled by an equivalent increase in the number o f mammary epithelial cells expressing cyclin D1. Conversely, under the same hormone regimen, the PRKO mammary gland did not exhibit a furthe r increase in cyclin D1 induction over estrogen only levels. Finally, these studies not only demonstrate that in the mammary epithelial cell , both estrogen and progesterone can induce the expression of cyclin D 1 but also show that this induction correlates with mammary gland prol iferation in the mouse.