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PMID: 2365825 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

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

The Journal of clinical investigation ·Vol. 86 ·No. 1 ·1990-07-00 ·Pages 356-62

Markowitz SD, Molkentin K, Gerbic C, Jackson J, Stellato T, Willson JK

Abstract

Autocrine stimulation of the epidermal growth factor receptor (EGF-R), by coexpression of transforming growth factor-alpha (TGF-alpha), causes malignant transformation of some fibroblast cell lines. TGF-alpha and EGF-R are both known to be expressed in colon carcinoma tissue and have been shown coexpressed in colon carcinoma cell lines. TGF-alpha 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-alpha 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-alpha and is completely abolished by a blocking anti-EGF-R antibody. Autocrine stimulation of EGF-R by TGF-alpha is therefore required for growth of the adenoma cell line. Autocrine stimulation of EGF-R by TGF-alpha does not cause malignant transformation of the colonic epithelial cell. In normal and adenomatous human colon TGF-alpha, via either an autocrine or paracrine mechanism, is likely an important physiologic stimulant of epithelial proliferation.

MeSH Terms
Adenoma/pathology Blotting, Northern Cell Division Cell Transformation, Neoplastic/genetics Colonic Neoplasms/pathology Epithelium/pathology ErbB Receptors/physiology Gene Expression Regulation Humans RNA, Messenger/genetics Transforming Growth Factors/physiology Tumor Cells, Cultured
Chemicals
RNA, Messenger Transforming Growth Factors ErbB Receptors
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Markowitz S D
Ireland Cancer Center, Case Western Reserve University, Cleveland, Ohio 44106.
Molkentin K
Gerbic C
Jackson J
Stellato T
Willson J K
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI114709
Published
1990-07-00
Pages
356-62
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC296730
Subset
IM
Grants
NCI NIH HHS · P30CA43703 · United States
NCI NIH HHS · U01-CA4596701 · United States
External Links
PubMed source DOI: 10.1172/JCI114709 PMC Full Text View journal details
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