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Growth control in a human colon carcinoma cell line mediated by cell-associated transforming growth factor-alpha (TGF

M A Zorbas1, L C Yeoman

  • 1Department of Pharmacology, Baylor College of Medicine, Houston, Texas 77030.

Experimental Cell Research
|May 1, 1993
PubMed

Insights

Cell-associated transforming growth factor-alpha (TGF alpha) on HCT116 colon cancer cells may drive autonomous growth via a closed autocrine loop with the epidermal growth factor (EGF) receptor. Elastase treatment released TGF alpha, restoring growth sensitivity.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • Transforming growth factor-alpha (TGF alpha) stimulates growth in cells with epidermal growth factor (EGF) receptors.
  • The TGF alpha precursor (proTGF alpha) is often uncleaved, accumulating on cell surfaces.
  • Cell-associated TGF alpha can promote growth in adjacent cells.

Purpose of the Study:

  • Investigate if cell-associated TGF alpha contributes to autonomous growth regulation in HCT116 colon carcinoma cells.
  • Determine the role of cell-associated TGF alpha in HCT116 cell growth.

Main Methods:

  • Quantified secreted and non-secreted TGF alpha in HCT116 cells at varying confluency.
  • Treated cells with porcine pancreatic elastase to release cell-associated TGF alpha.
  • Analyzed EGF receptor phosphotyrosine levels via Western blot.

Main Results:

  • HCT116 cells showed maximum cell-associated TGF alpha (50%) at medium confluency.
  • Elastase released 67% of cell-associated TGF alpha, increasing sensitivity to exogenous TGF alpha.
  • EGF receptor phosphotyrosine levels decreased after elastase treatment, restored by exogenous TGF alpha or EGF.

Conclusions:

  • HCT116 cells utilize a closed autocrine loop involving cell-associated TGF alpha and EGF receptors for growth stimulation.
  • This mechanism suggests a novel pathway for autonomous cell growth regulation in colon cancer.

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