Regulation of autocrine gastrin expression by the TGFα autocrine loop

Gillian M. Howell, Barry L. Ziober, Lisa E. Humphrey, James K V Willson, Luzhe Sun, Mark Lynch, Michael G. Brattain

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26 Scopus citations

Abstract

Gastrin is transcriptionally responsive to EGF stimulation (Merchant et al., 1991, Mol. Cell. Biol., 11:2686-2696). Consequently, we hypothesized that previously recognized gastrin autocrine loops (Hoosein et al., 1990, Exp. Cell. Res., 186:15-21), might be controlled by autocrine TGFα in human colon carcinoma cells. Therefore, we examined the interaction between these two autocrine growth factors in two colon carcinoma cell lines which utilize TGFα. The FET cell line requires exogenous TGFα/EGF for optimal growth and has a classical TGFα autocrine loop which is disrupted by TGFα or epidermal growth factor receptor (EGFr) antibodies. The HCT 116 cell line is not dependent on exogenous TGFα/EGF and exhibits a nonclassical TGFα autocrine loop which is not disrupted by neutralizing antibodies to either TGFα itself or the EGFr. Basal gastrin mRNA production is significantly higher in HCT 116 than FET as measured by RNase protection assay. In the FET cells, exogenous EGF stimulates gastrin mRNA production but not in HCT 116. When the TGFα autocrine loop in HCT 116 is disrupted by constitutive expression of antisense TGFα mRNA, the gastrin mRNA level is significantly repressed. In xenografts derived from these antisense clones, TGFα reverted to high expression, and the gastrin mRNA-level was again increased. This interaction between the strong TGFα loop in HCT 116 and the gastrin autocrine loop may confer a growth advantage to these colon cells. Such interactions between growth factors may promote enhanced tumorigenicity to transformed cells with these strong, nonclassical autocrine loops.

Original languageEnglish (US)
Pages (from-to)256-265
Number of pages10
JournalJournal of Cellular Physiology
Volume162
Issue number2
DOIs
Publication statusPublished - Feb 1995

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ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology

Cite this

Howell, G. M., Ziober, B. L., Humphrey, L. E., Willson, J. K. V., Sun, L., Lynch, M., & Brattain, M. G. (1995). Regulation of autocrine gastrin expression by the TGFα autocrine loop. Journal of Cellular Physiology, 162(2), 256-265. https://doi.org/10.1002/jcp.1041620211