Growth Regulation of A431 Cells MODULATION OF EXPRESSION OF TRANSFORMING GROWTH FACTOR-a mRNA

To explore bidirectional regulatory interactions between interferons and autocrine polypeptide factors, we examined the modulation of expression of transforming growth factor-a and 2’,5’-oligoadenylate synthetase activity in A431 epidermoid carcinoma cells after treatment with interferon-y and transforming growth factor-a. Treatment of A431 cells with interferon-y increased steady state levels of transforming growth factor-a mRNA by 4-fold and increased the levels of transforming growth factor-a in the culture medium. There were additive growth inhibitory effects upon coaddition of exogenous transforming growth factor-a and interferon-y to the cultures. Addition of transforming growth factor-a to A431 cell cultures in the absence of interferon could stimulate the induction of 2’,5’-oligoadenylate synthetase activity by more than a-fold. These findings demonstrate that the induction of transforming growth factor-a in interferony-treated A431 cells could act to regulate interferoninduced gene(s), e.g. 2’,5’-oligoadenylate synthetase, suggesting interactions between a potential autocrine growth factor and the interferon system in the growth regulation of A43 1 cells.