Up-regulation of transforming growth factor alpha expression by transforming growth factor beta 1, epidermal growth...

This report examines the effects of inhibitors of cell proliferation on transforming growth factor alpha (TGF-alpha) expression in low-density cultures of poorly (PD) and well-differentiated (WD) human colon carcinoma cells, continuously maintained in serum-free medium. In contrast to results in certain untransformed cells, growth inhibitors such as transforming growth factor beta 1 (TGF-beta 1) and N,N-dimethylformamide up-regulated TGF-alpha mRNA and protein expression in these human colon carcinoma cells. Treatment of low-density WD cells with TGF-beta 1 (10 ng/ml) resulted in a 1.5-fold increase in TGF-alpha mRNA levels within 4 h of treatment. TGF-alpha mRNA levels increased to 2.7-fold above control values by 48 h after TGF-beta 1 addition. Additionally, over a TGF-beta 1 concentration range of 1-30 ng/ml, TGF-alpha protein levels were increased by 2-10-fold, despite the fact that the growth of the WD cells remained inhibited. Although TGF-beta 1 control of TGF-alpha expression was altered in these WD colon carcinoma cells, relative to that in untransformed cells previously examined, the cells retained the ability to up-regulate TGF-alpha expression in an epidermal growth factor-dependent manner. In similarity to the results with TGF-beta 1 in WD colon carcinoma cells, the differentiation agent N,N-dimethylformamide (0.7%) resulted in an increase of TGF-alpha mRNA of approximately 3.8-fold in PD colon carcinoma cells, as well as a 4.4-fold increase in TGF-alpha protein after 4 days of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)