Two roles for transforming growth factor beta 1 in colon enterocytic cell differentiation.

M. M. Hafez, Stephen Hsu, Z. Yan, S. Winawer, E. Friedman

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The role of transforming growth factor beta 1 (TGF-beta 1) in enterocytic differentiation was examined by treating two undifferentiated HT29 colon carcinoma sublines, U4 and U9, with hexamethylene bisacetamide to up-regulate their level of TGF-beta 1 mRNA expression. Although both lines after treatment secreted approximately equal levels of biologically active TGF-beta 1, only U4H cells were found to undergo enterocytic differentiation when cultured postconfluence on collagen I-coated transwells, forming polarized monolayer cells with an apical brush border, whereas U9H cells remained multilayered and undifferentiated. Enterocytic U4H cells exhibited four times as much cell surface expression of the collagen I-binding protein alpha 2-integrin, twice as much of the accessory collagen-binding protein carcinoembryonic antigen, and almost twice as much binding to collagen I films as undifferentiated U9H cells. TGF-beta 1 treatment doubled U4 cell collagen I binding, increased expression of alpha 2-integrin 4-fold, but increased carcinoembryonic antigen expression only marginally. U4H cells displayed cell cycle regulation by arresting reversibly at a restriction point in G1 when placed in the postconfluent culture conditions which initiated enterocytic differentiation. In contrast, undifferentiated U9H cells exhibited no restriction point but arrested throughout G1. TGF-beta 1 blocked synchronized U4H cells in G1, whereas it stimulated the growth of U9H cells. Thus, TGF-beta 1 has two roles in enterocytic differentiation: to increase levels of collagen I adhesion proteins and to block enterocytic cells in G1 so that they can differentiate.

Original languageEnglish (US)
Pages (from-to)753-762
Number of pages10
JournalCell growth & differentiation : the molecular biology journal of the American Association for Cancer Research
Volume3
Issue number11
StatePublished - Jan 1 1992
Externally publishedYes

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Transforming Growth Factor beta
Cell Differentiation
Colon
Collagen
Integrin alpha Chains
Carcinoembryonic Antigen
hexamethylene bisacetamide
Carrier Proteins
G1 Phase Cell Cycle Checkpoints
Microvilli
Cell Cycle
Up-Regulation
Carcinoma
Messenger RNA

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Two roles for transforming growth factor beta 1 in colon enterocytic cell differentiation. / Hafez, M. M.; Hsu, Stephen; Yan, Z.; Winawer, S.; Friedman, E.

In: Cell growth & differentiation : the molecular biology journal of the American Association for Cancer Research, Vol. 3, No. 11, 01.01.1992, p. 753-762.

Research output: Contribution to journalArticle

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