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J. Biol. Chem., Vol. 277, Issue 1, 75-86, January 4, 2002
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From the Despite constitutive expression of autocrine
transforming growth factor-
Differences in Sensitivity of Biological Functions Mediated by
Epidermal Growth Factor Receptor Activation with Respect to Endogenous
and Exogenous Ligands*
,,
,**
Department of Pharmacology & Therapeutics,
Roswell Park Cancer Institute, Buffalo, New York 14263, the
¶ Department of Surgery, University of Texas Health Science
Center, San Antonio, Texas 78229, and the § Department of
Pharmacology, Baylor College of Medicine, Houston, Texas 77030
(TGF-) in growth
factor-independent colon carcinoma cells, the epidermal growth factor
receptor (EGFr) is not saturated and can be further activated by
exogenous EGFr ligand. Given that the activation of EGFr by exogenous
growth factor has no further effect on DNA synthesis, the question
arises as to what function this additional EGFr activation might have.
We report that EGF induces integrin 2 expression,
integrin-mediated adhesion, and micromotility of HCT116 cells. The
stimulatory effect of ligand on these biological functions is abrogated
by treatment with AG1478- and EGFr-blocking monoclonal antibody. This
provides evidence that the biological responses are EGFr-mediated and
EGFr is located upstream of integrin 2 expression.
Therefore, although exogenous EGF has no effect on DNA synthesis beyond
that induced by autocrine TGF- (at subsaturating levels of EGFr
occupation) exogenous growth factor does induce integrin
2 expression, cell adhesion, and micromotion. An
important finding revealed by this study is the documentation of
biological responses of EGFr-mediated functions, including DNA
synthesis, cell adhesion, and micromotion, which differ in sensitivity
with respect to different degrees of EGFr activation at the basal state
and in response to exogenous ligand.
*
This work was supported in part by National Institutes of
Health Grants CA 54807, 34432, 50457, and HL07446, by a Merit Review from the Veterans Administration, and by the Shelby Rae Tengg Foundation.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Supported by the Veterans Administration grant.
**
To whom correspondence should be addressed: Dept. of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, NY 14263.
Tel.: 716-845-3044; Fax: 716-845-8857; E-mail:
michael.brattain@roswellpark.org.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
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