GROWTH-STIMULATION BY COEXPRESSION OF TRANSFORMING GROWTH FACTOR-ALPHA AND EPIDERMAL GROWTH FACTOR-RECEPTOR IN NORMAL AND ADENOMATOUS HUMAN COLON EPITHELIUM

Autocrine stimulation of the epidermal growth factor receptor (EGF-R), by coexpression of transforming growth factor-α (TGF-α), causes malignant transformation of some fibroblast cell lines. TGF-α and EGF-R are both known to be expressed in colon carcinoma tissue and have been shown coexpressed in colon carcinoma cell lines. TGF-α autocrine activation of EGF-R has been suggested as a potential mechanism contributing to abnormal growth control in colon cancer. We now report coexpression of TGF-α and EGF-R transcripts in morphologically normal colonic epithelium from five individuals, in colonic adenomas from three individuals, and in a nontumorigenic colon adenoma cell line, VACO-330. Functional studies demonstrate VACO-330 growth is stimulated by exogenous TGF-α and is completely abolished by a blocking anti-EGF-R antibody. Autocrine stimulation of EGF-R by TGF-α is therefore required for growth of the adenoma cell line. Autocrine stimulation of EGF-R by TGF-α does not cause malignant transformation of the colonic epithelial cell. In normal and adenomatous human colon TGF-α, via either an autocrine or paracrine mechanism, is likely an important physiologic stimulant of epithelial proliferation.