Evidence for c‐myc in the signaling pathway for TGF‐β in well‐differentiated human colon carcinoma cells

Kathleen Mulder, Lisa E. Humphrey, Ho Gene Choi, Karla E. Childress‐Fields, Michael G. Brattain

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26 Citations (Scopus)

Abstract

Previously, we described a model culture system for comparing responsiveness of poorly differentiated and well‐differentiated human colon carcinoma cells to exogenous growth factors. While polypeptide growth stimulators elicited an up‐regulation of c‐myc, as well as a mitogenic response in the well‐differentiated cells, the poorly differentiated cells were insensitive to exogenous growth stimulators. We now show, by thymidine incorporation experiments and autoradiographic analysis, that transforming growth factors, β1 (TGF‐β) abrogated the mitogenic responses to the growth factors epidermal growth factor + insulin + transferrin (lC,50 = 0.8 ng/ml), as well as to nutrients (basal medium; lC50 = 0.2 ng/ml) in the well‐differentiated cells. The poorly differentiated cells did not respond to TGF‐β. Moreover, TGF‐β (10 ng/ml) completely abrogated the growth factor‐stimulated up‐regulation of c‐myc in the TGF‐β responsive, well‐differentiated colon carcinoma cells. Addition of TGF‐β to the TGF‐β‐responsive, well‐differentiated cells, at a time after c‐myc had been transiently up‐regulated in response to growth stimulatory factors, resulted in a loss of responsiveness to TGF‐β. Addition of TGF‐β to these cells at increasing time periods after EIT stimulation also resulted in a loss of the TGF‐β‐induced repression of c‐myc. The results suggest an important role for c‐myc in the mechanism of action of TGF‐β in well‐differentiated human colon carcinoma cells.

Original languageEnglish (US)
Pages (from-to)501-507
Number of pages7
JournalJournal of Cellular Physiology
Volume145
Issue number3
DOIs
StatePublished - Jan 1 1990

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Transforming Growth Factors
Colon
Cells
Carcinoma
Intercellular Signaling Peptides and Proteins
Up-Regulation
Growth
Transferrin
Cell culture
Epidermal Growth Factor
Thymidine
Nutrients
Insulin
Peptides
Food

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Mulder, Kathleen ; Humphrey, Lisa E. ; Choi, Ho Gene ; Childress‐Fields, Karla E. ; Brattain, Michael G. / Evidence for c‐myc in the signaling pathway for TGF‐β in well‐differentiated human colon carcinoma cells. In: Journal of Cellular Physiology. 1990 ; Vol. 145, No. 3. pp. 501-507.
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Evidence for c‐myc in the signaling pathway for TGF‐β in well‐differentiated human colon carcinoma cells. / Mulder, Kathleen; Humphrey, Lisa E.; Choi, Ho Gene; Childress‐Fields, Karla E.; Brattain, Michael G.

In: Journal of Cellular Physiology, Vol. 145, No. 3, 01.01.1990, p. 501-507.

Research output: Contribution to journalArticle

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AU - Humphrey, Lisa E.

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