| Abstract: |
Abnormalities in the expression, structure, or activity of proto-oncogene products have been implicated in the development and maintenance of the malignant cells. Protooncogene c-erbB2/HER2 gene product P185(HER2) is one such regulatory cellular protein, elevated expression of which can result in transformed phenotypes of mouse fibroblast NIH3T3 cells, and has been also shown to be overexpressed in a number of human tumors including breast carcinoma. In the studies presented here, we have investigated the effects of antiproliferative cytokines such as interferons (INFs) and tumor necrosis factor-alpha (TNF-alpha) on, the modulation of expression of P185(HER2) and growth-rate of human mammary carcinoma SK-BR-3 cells which overexpress P185(HER2). It was observed that the antiproliferative effects of IPN-gamma and TNF-alpha on the cultures of SK-BR-3 cells were associated with reduction in the steady-state levels of P185(HER2) With 110 change in the steady state levels of expression of c-erbB2 mRNA. Treatment of SK-BR-3 cells with either IFN-gamma or TNF-alpha was accompanied by inhibition of rate of synthesis of the protein, enhanced turnover of newly synthesized P185(HER2), and reduced expression of P185(HER2) On the cell surface. These observed effects on the expression of P185(HER2) were more pronounced by more growth inhibitory TNF-alpha than IFN-gamma. These observations suggest that the growth regulation of SK-BR-3 cells by IFN-gamma and TNF-alpha may be associated with reduced expression P185(HER2). |
