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 language | English (US) |
|---|---|
| Pages (from-to) | 356-362 |
| Number of pages | 7 |
| Journal | Journal of Clinical Investigation |
| Volume | 86 |
| Issue number | 1 |
| State | Published - Jul 1990 |
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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 journal › Article
}
TY - JOUR
T1 - Growth stimulation by coexpression of transforming growth factor-α and epidermal growth factor-receptor in normal and adenomatous human colon epithelium
AU - Markowitz, Sanford D.
AU - Molkentin, Kay
AU - Gerbic, Catherine
AU - Jackson, Julie
AU - Stellato, Thomas
AU - Willson, James K V
PY - 1990/7
Y1 - 1990/7
N2 - 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.
AB - 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.
KW - Autocrine
KW - Colon
KW - Transforming growth factors
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UR - http://www.scopus.com/inward/citedby.url?scp=0025368610&partnerID=8YFLogxK
M3 - Article
C2 - 2365825
AN - SCOPUS:0025368610
VL - 86
SP - 356
EP - 362
JO - Journal of Clinical Investigation
JF - Journal of Clinical Investigation
SN - 0021-9738
IS - 1
ER -