Inhibitory effects of transforming growth factor β1 on mitogenic response, transforming growth factor a, and c-myc in quiescent, well-differentiated colon carcinoma cells

Kathleen M. Mulder, Qing Zhong, Ho Gene Choi, Lisa E. Humphrey, Michael G. Brattain

Research output: Contribution to journalArticle

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Abstract

Previously, we reported that exponentially proliferating cultures of well-differentiated human colon carcinoma cells responded to transforming growth factor β1 (TGF-β) with growth inhibition, alterations in morphology, and increased secretion of the differentiation marker, carcinoembryonic antigen. Poorly differentiated cultures were unresponsive. Here we show that TGF-β was ineffective in repressing nutrient-stimulated mitogenesis in quiescent, poorly differentiated cells. However, in quiescent, well-differentiated cells, TGF-β repressed the mitogenic responses to both nutrients alone (by 90%) and to nutrients plus the exogenous stimulatory factors epidermal growth factor (E), insulin (I), and transferrin (T) (by 55-65%). Thymidine incorporation experiments indicated that TGF-β reduced both the onset and peak mitogenic response to growth factors and/or nutrients in the well-differentiated cells. Additionally, TGF-β repressed the growth factor (E + I + T)-stimulated up-regulation of expression of both c-myc and of transforming growth factor α (TGF-α) mRNAs in quiescent, well-differentiated cells. TGF-β also elicited a rapid (t1/2 ≈1h) down-regulation of c-myc expression in the absence of prior growth factor (E + I + T) stimulation. In contrast, TGF-β had no effect on c-myc or TGF-α mRNA expression in the poorly differentiated cells. The results suggest that TGF-β exerts rapid inhibitory effects on proliferation-associated genes in quiescent and restimulated, well-differentiated cells. Expression of these genes (c-myc and TGF-α) may otherwise (in the absence of TGF-β) play roles in the cellular signaling of mitogenic responses by growth stimulatory factors in well-differentiated colon carcinoma cells.

Original languageEnglish (US)
Pages (from-to)7581-7586
Number of pages6
JournalCancer Research
Volume50
Issue number23
StatePublished - Dec 1 1990
Externally publishedYes

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Transforming Growth Factors
Colon
Carcinoma
Intercellular Signaling Peptides and Proteins
Food
Differentiation Antigens
Messenger RNA
myc Genes
Carcinoembryonic Antigen
Transferrin
Epidermal Growth Factor
Thymidine
Up-Regulation
Down-Regulation
Insulin

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Inhibitory effects of transforming growth factor β1 on mitogenic response, transforming growth factor a, and c-myc in quiescent, well-differentiated colon carcinoma cells. / Mulder, Kathleen M.; Zhong, Qing; Choi, Ho Gene; Humphrey, Lisa E.; Brattain, Michael G.

In: Cancer Research, Vol. 50, No. 23, 01.12.1990, p. 7581-7586.

Research output: Contribution to journalArticle

Mulder, Kathleen M. ; Zhong, Qing ; Choi, Ho Gene ; Humphrey, Lisa E. ; Brattain, Michael G. / Inhibitory effects of transforming growth factor β1 on mitogenic response, transforming growth factor a, and c-myc in quiescent, well-differentiated colon carcinoma cells. In: Cancer Research. 1990 ; Vol. 50, No. 23. pp. 7581-7586.
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abstract = "Previously, we reported that exponentially proliferating cultures of well-differentiated human colon carcinoma cells responded to transforming growth factor β1 (TGF-β) with growth inhibition, alterations in morphology, and increased secretion of the differentiation marker, carcinoembryonic antigen. Poorly differentiated cultures were unresponsive. Here we show that TGF-β was ineffective in repressing nutrient-stimulated mitogenesis in quiescent, poorly differentiated cells. However, in quiescent, well-differentiated cells, TGF-β repressed the mitogenic responses to both nutrients alone (by 90{\%}) and to nutrients plus the exogenous stimulatory factors epidermal growth factor (E), insulin (I), and transferrin (T) (by 55-65{\%}). Thymidine incorporation experiments indicated that TGF-β reduced both the onset and peak mitogenic response to growth factors and/or nutrients in the well-differentiated cells. Additionally, TGF-β repressed the growth factor (E + I + T)-stimulated up-regulation of expression of both c-myc and of transforming growth factor α (TGF-α) mRNAs in quiescent, well-differentiated cells. TGF-β also elicited a rapid (t1/2 ≈1h) down-regulation of c-myc expression in the absence of prior growth factor (E + I + T) stimulation. In contrast, TGF-β had no effect on c-myc or TGF-α mRNA expression in the poorly differentiated cells. The results suggest that TGF-β exerts rapid inhibitory effects on proliferation-associated genes in quiescent and restimulated, well-differentiated cells. Expression of these genes (c-myc and TGF-α) may otherwise (in the absence of TGF-β) play roles in the cellular signaling of mitogenic responses by growth stimulatory factors in well-differentiated colon carcinoma cells.",
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