Growth stimulation by coexpression of transforming growth factor-α and epidermal growth factor-receptor in normal and adenomatous human colon epithelium

Sanford D. Markowitz, Kay Molkentin, Catherine Gerbic, Julie Jackson, Thomas Stellato, James K V Willson

Research output: Contribution to journalArticle

131 Citations (Scopus)

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 colonie 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 languageEnglish (US)
Pages (from-to)356-362
Number of pages7
JournalJournal of Clinical Investigation
Volume86
Issue number1
StatePublished - Jul 1990

Fingerprint

Transforming Growth Factors
Epidermal Growth Factor Receptor
Colon
Epithelium
Growth
Adenoma
Cell Line
Carcinoma
Colonic Neoplasms
Fibroblasts
Epithelial Cells
Antibodies

Keywords

  • Autocrine
  • Colon
  • Transforming growth factors

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Growth stimulation by coexpression of transforming growth factor-α and epidermal growth factor-receptor in normal and adenomatous human colon epithelium. / Markowitz, Sanford D.; Molkentin, Kay; Gerbic, Catherine; Jackson, Julie; Stellato, Thomas; Willson, James K V.

In: Journal of Clinical Investigation, Vol. 86, No. 1, 07.1990, p. 356-362.

Research output: Contribution to journalArticle

Markowitz, Sanford D. ; Molkentin, Kay ; Gerbic, Catherine ; Jackson, Julie ; Stellato, Thomas ; Willson, James K V. / Growth stimulation by coexpression of transforming growth factor-α and epidermal growth factor-receptor in normal and adenomatous human colon epithelium. In: Journal of Clinical Investigation. 1990 ; Vol. 86, No. 1. pp. 356-362.
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