Impact of C-neu/erbB2 on Estrogen and Estrogen Receptor Alpha-Dependent Proliferation of Mammary Ductal Epithelial Cells

摘要

The objective of our research is to examine the expression patterns of estrogen receptor (ER-alpha), progesterone receptor (PR) and C-Neu in mammary glands of wild type and C-Neu transgenic mice during various developmental states and identify the relationships between these expression patterns to cells undergoing proliferation. In previous studies, we demonstrated that there were differences between the mammary glands of wild type and C-Neu mice with regard to their expression patterns of PR. And were apparent as early as six weeks of age. Our present studies reveal that mammary glands of c-neu mice contain abnormal structures with a high rate of proliferation and also that this is ovarian steroid/estrogen independent and detectable as early as 6 weeks of age. The average onset of mammary tumors in c-neu mice is approximately 30-32 weeks Yet, our studies, so far, indicate that c-neu dependent alterations in ovarian steroid hormonal regulation of mammary epithelial cells represent early events and not a late phenomenon associated with tumor progression We propose that estrogen independent proliferation may be intrinsic to mammary cells that over express c-neu. If so, both blocking erbB2 activity and the use of appropriate SERMS may be more beneficial in the clinical management of c-neu cancers.