| Popis: |
Our laboratory has shown that TNF can regulate normal mammary epithelial cell (MEC) growth, morphogenesis, and, under certain circumstances, functional differentiation in a manner similar to LGF. Since INF has been shown to up-regulate EGF receptor (EGFR) expression and function in other systems, the current studies were undertaken to determine whether TNF action in MEC was indirect through-stimulation of the EGFR. An inhibitor of EGFR tyrosine kinase activity, PDl58780, failed to block proliferation induced by 40 ng/ml TNF and only partially inhibited growth in response to 2 ng/ml TNF. PD158780 was also unable to suppress the extensive morphological development induced by either TNF concentration. In contrast, the effects of TNF and PDl58780 on functional differentiation (i.e. casein accumulation) were time-dependent. When measured on day 7 after 48 hours of treatment, casein accumulation was unaffected by either concentration of TNF or by PDl5S7SO. When assessed on day 21 after 16 days of treatment, however, casein levels were decreased by 40 ng/ml TNF and increased by PD158780. Significantly, this PD158780-induced increase in casein was not observed in MEC which had been treated with both PD158780 and TNF. These results thus suggest that EGFR tyrosine kinase activity is not necessary for TNF action in normal MEC. |
