The Role and Regulation of TNF-alpha in Normal Rat Mammary Gland During Development and in Breast Cancer.
HEALTH RESEARCH INC BUFFALO NY
Pagination or Media Count:
The pleiotropic cytokine tumor necrosis factor a TNFa has previously been shown to regulate both the proliferation and differentiation of normal rat mammary epithelial cells MEC in primary culture Ip et al, Endocrinology, 130, 2833-2844, 1992. Using agonistic antibodies Genentech specific to either the p55 or p75 TNF receptors, the individual roles of each TNF receptor in signalling these cellular responses was investigated. Under suboptimal low EGF, 0.1 ngml medium conditions in which TNFa can substitute for EGF for cell proliferation, the p55 receptor was found to be the sole mediator of TNFa-induced proliferation of MEC. Unexpectedly, antibodies directed against either TNF receptor had equivalent stimulatory effects on alveolar morphogenesis in suboptimal medium. Furthermore, the two receptors were found to have opposing effects on functional differentiation as assessed by casein accumulation. In both optimal 10 ngml EGF and suboptimal media conditions, casein accumulation was inhibited in response to the p55 antibody, while it was stimulated by the antibody against the p75 receptor. Thus, these studies demonstrate that both TNF receptors are important for TNFa function in the mammary gland.
- Medicine and Medical Research