Impact of C-neu/erbB2 on Estrogen and Estrogen Receptor Alpha-Dependent Proliferation of Mammary Ductal Epithelial Cells
Annual rept. 4 Sep 2001-3 Sep 2002
CALIFORNIA UNIV BERKELEY LAWRENCE BERKELEY LAB
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Estrogen and progesterone, signaling through their cognate receptors- ER and PR, respectively, promote the growth of mammary glands via growth factors which signal through the family of erbB receptors, such as C- neuerbB2. We have made the paradoxical observation that in transgenic mice overexpressing C-neu, in which mammary tumors arise, mammary growth is, in fact, compromised during puberty without any gross impairment in growth during pregnancy. Our hypothesis is that a the individual and combined effects of ER, PR andor C- neu depends on the mammary epithelial sub-type and the interactions among these receptors, bthe net outcome of these interactions is to direct the developmental fate of the various epithelial subclasses and c a perturbation in these interactions, resulting from either an altered expression or signaling through these receptors leads to aberrant morphogenesis and neoplasia. Accordingly, we propose 1 To examine the expression patterns of ER, PR and C-neu in mammary glands of wild type and C-neu transgenic mice during various developmental states and their relationships to cells undergoing proliferation and, 2 To examine the growth patterns of mammary glands of C-neu transgenic mice upon serial transplantation into de-epithelialized fat pads. Our proposed studies will identify changes conducive to tumorigenesis, occurring in response to C-neu over- expression during early mammary development this, in turn, can help to devise prophylatic strategies aimed at prevention and hence, its significance.
- Anatomy and Physiology
- Medicine and Medical Research