Ductal growth is impeded in mammary glands of C-neu transgenic mice

The steroid hormone, estradiol, is essential for both the growth of normal breast and induction of mammary carcinomas, The growth promoting effects of estrogen are presumed to be mediated by growth factors, in particular, epi dermal growth factor, which mediates its effects through erbB receptors, er bB1 and erbB2/C-neu. C-neu is amplified and over-expressed in a large numbe r of human cancers and transgenic mice over-expressing C-neu also develop m ammary tumors, However, as set, the impact of C-neu over-expression on estr ogen action during normal mammary development and hence, its precise role i n carcinogenesis, remains unclear, In the present studies, we demonstrate t hat estradiol-dependent mammary ductal growth accompanying puberty is impai red in transgenic mice expressing wild type C-neu, and is intrinsic to the tissue. The impairment is not due to an overall impairment in estrogen acti on, since progesterone receptor expression is unaffected in C-neu mice. It is also not due to an intrinsic inability of the epithelial cells to prolif erate, since impeded ductal growth co-exists,vith alveolar growth during pr egnancy. Therefore, we propose that, depending on the physiological state, C-neu may either promote or inhibit the growth of mammary epithelial cells, and discuss its potential significance to carcinogenesis.