Experiments are being conducted to determine the distribution and role of alpha transforming growth factors (AlphaTGFs) in normal and malignant rodent and human mammary epithelial cells. Primary dimethylbenz(Alpha)anthracene (DMBA) and nitrosomethylurea (NMU) rat mammary adenocarcinomas possess three to seven-fold more biologically active and immunoreactive AlphaTGFs than transplantable DMBA-I and NMU-II carcinomas. Moreover, a specific 5.0 kb mRNA species could be detected in the primary DMBA and NMU tumors following hybridization of poly A(+) RNA to a human and mouse AlphaTGF cDNA probes but not in the DMBA-I or NMU-II tumors. Ovariectomy produced a two to three-fold decrease in the level of AlphaTGFs in the primary DMBA tumors which was preceeded by a loss in the expression of AlphaTGF mRNA. Mouse mammary epithelial which have been transformed with a point-mutated c-Ha-ras proto-oncogene, NMuMG/rasH cells, become resistant to the growth promoting effects of EGF because these cells have an increased capacity to synthesize AlphaTGF mRNA. Human breast cancer cell lines are also producing AlphaTGF and possess AlphaTGF mRNA. In MCF-7 cells, the level of production of AlphaTGF can be enhanced by estrogens. Elevated levels of immunoreactive AlphaTGF and AlphaTGF mRNA can be detected in approximately 50% of primary human breast carcinomas. There is a strong positive correlation between the presence of AlphaTGF mRNA and the presence of functional estrogen receptors in a subset of these tumors.
