Expression of TGFα autocrine activity in human colon carcinoma CBS cells is autoregulated and independent of exogenous epidermal growth factor

Dianhua Jiang, Jiurong Liang, Lisa E. Humphrey, Haisu Yang, Michael G. Brattain

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Autocrine transforming growth factor a (TGFα) activity and control mechanisms for its expression were examined in a representative clonal isolate (CBS4) of a well-differentiated human colon carcinoma cell line designated CBS. CBS4 cells expressed TGFα and its receptor, epidermal growth factor receptor (EGFr). Blockade of EGFr and TGFα by neutralizing antibodies inhibited clonal growth and the initiation of DNA synthesis from quiescence in CBS4 cells. Therefore, TGFα is an autocrine growth factor for CBS4 cells. Several studies have indicated that activation of the EGFr by exogenous EGF stimulates TGFα expression. However, in CBS4 cells EGF did not induce TGFα mRNA expression, indicating that EGF does not affect TGFα transcription in these cells. Exogenous treatment of exponentially growing cells with either EGF or EGFr blocking antibody enhanced release of TGFα protein into the conditioned medium. This indicated that the release of TGFα into the conditioned medium by exogenous EGF was at least partially due to the displacement of TGFα from the TGFα/EGFr complexes. Similarly to exponentially growing cells, the EGFr blocking antibody and EGF also enhanced TGFα release into the medium of CBS4 cells after release from quiescence. These results indicated that exogenous EGF had little if any effect on TGFα expression in these cells and suggested that TGFα expression might be under endogenous TGFα control. Blockade of the autocrine TGFα loop by TGFα neutralizing antibody suppressed TGFα mRNA both in exponentially growing and quiescent cells, demonstrating that autocrine TGFα is autoregulatory in this system.

Original languageEnglish (US)
Pages (from-to)174-183
Number of pages10
JournalJournal of Cellular Physiology
Volume175
Issue number2
DOIs
StatePublished - May 1998

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

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