Differences in sensitivity of biological functions mediated by epidermal growth factor receptor activation with respect to endogenous and exogenous ligands

Rajinder S. Sawhney, Guo Hao K. Zhou, Lisa E. Humphrey, Paramita Ghosh, Jeffrey I. Kreisberg, Michael G. Brattain

Research output: Contribution to journalArticlepeer-review

34 Scopus citations

Abstract

Despite constitutive expression of autocrine transforming growth factor-α (TGF-α) 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 α2 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 α2 expression. Therefore, although exogenous EGF has no effect on DNA synthesis beyond that induced by autocrine TGF-α (at subsaturating levels of EGFr occupation) exogenous growth factor does induce integrin α2 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.

Original languageEnglish (US)
Pages (from-to)75-86
Number of pages12
JournalJournal of Biological Chemistry
Volume277
Issue number1
DOIs
StatePublished - Jan 4 2002

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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