Transforming Growth Factor-α1 Induces Transforming Growth factor-α Promoter Activity and Transforming Growth Factor-α Secretion in the Human Colon Adenocarcinoma Cell Line FET

Mark J. Lynch, Lenore Pelosi, Joan M. Carboni, June Merwin, Kevin Coleman, Richard R.C. Wang, Pin Fang M. Lin, Diane L. Henry

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

FET cells are well differentiated human adenocarcinoma cells whose growth is partially inhibited (50-60%) by transforming growth factor-α1 (TGF-β1). In exponentially growing cultures, TGF-β1 induces the expression of transforming growth factor-α (TGF-α) by 3-fold. To determine whether this induction is the result of increased TGF-α promoter activity, FET cells were transiently transfected with a plasmid containing 2816 base pairs of the 52-flanking region of the TGF-α gene linked to luciferase. Transfected FET cells treated with growth-inhibitory concentrations of TGF-β1 (10 ng/ml) showed up to a 10-fold increase in luciferase activity. The increase in luciferase activity was dose dependent through the normal physiological range of TGF-β1 (0.5-20 ng/ml), saturating at 10 ng/ml. This effect was also TGF-α promoter specific, inasmuch as the Rous sarcoma virus long terminal repeat used as a control remained relatively insensitive to the effects of TGF-β1. By using progressively smaller portions of the TGF-α promoter region, the TGF-β1-responsive element was mapped between base pairs -77 and -201 of the 52-flanking region. TGF-β1 treatment also affected epidermal growth factor receptor levels. FET cells treated with TGF-β1 (10 ng/ml) for 48 h showed a 20% decrease in the number of epidermal growth factor receptors and a 2-fold increase in the number of high affinity epidermal growth factor receptors on their surface. These results indicate that TGF-β1 acts as a positive regulator of TGF-α transcription, and they suggest a possible mechanism by which these cells circumvent the growth-inhibitory effects of TGF-β1.

Original languageEnglish (US)
Pages (from-to)4041-4047
Number of pages7
JournalCancer Research
Volume53
Issue number17
StatePublished - Sep 1993

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Lynch, M. J., Pelosi, L., Carboni, J. M., Merwin, J., Coleman, K., Wang, R. R. C., Lin, P. F. M., & Henry, D. L. (1993). Transforming Growth Factor-α1 Induces Transforming Growth factor-α Promoter Activity and Transforming Growth Factor-α Secretion in the Human Colon Adenocarcinoma Cell Line FET. Cancer Research, 53(17), 4041-4047.