Abstract
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.
Original language | English (US) |
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Pages (from-to) | 356-362 |
Number of pages | 7 |
Journal | Journal of Clinical Investigation |
Volume | 86 |
Issue number | 1 |
DOIs | |
State | Published - 1990 |
Keywords
- autocrine
- colon
- transforming growth factors
ASJC Scopus subject areas
- Medicine(all)