Expression of transforming growth factor alpha (TGFα) in breast cancer

Summary Transforming growth factor alpha (TGFα) is one growth factor that has been circumstantially implicated in regulating the autocrine growth of breast cancer cells. Expression of TGFα can be modulated by activated cellular protooncogenes such as ras and by estrogens. For example, the epidermal growth factor (EGF)-responsive normal NOG-8 mouse and human MCF-10A mammary epithelial cell lines can be transformed with either a point-mutated c-Ha-ras protooncogene or with a normal or point-mutated c-neu (erbB-2) protoonco-gene. In ras transformed NOG-8 and MCF-10A cells but not in neu transformed cells there is a loss in or an attenuated response to the mitogenic effects of EGF. This response may be due in part to an enhanced production of endogenous TGFα that is coordinately and temporally linked to the expression of the activated ras gene and to the acquisition of transformation-associated properties in these cells. TGFα mRNA and TGFα protein can also be detected in approximately 50–70% of primary human breast tumors. In addition, approximately 2- to 3-fold higher levels of biologically active and immunoreactive TGFα can also be detected in the pleural effusions from breast cancer patients as compared with the TGFa levels in the serous effusions of noncancer patients. Over-expression of a full-length TGFα cDNA in NOG-8 and MCF-10A cells is capable of transforming these cells. Finally, expression of TGFα mRNA and production of biologically active TGFα protein is also found in normal rodent and human mammary epithelial cells.