Two roles for transforming growth factor ß(1) in colon enterocytic cell differentiation Journal Article


Authors: Hafez, M. M.; Hsu, S.; Yan, Z.; Winawer, S.; Friedman, E.
Article Title: Two roles for transforming growth factor ß(1) in colon enterocytic cell differentiation
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.
Keywords: comparative study; cytology; transforming growth factor beta; carcinoembryonic antigen; neoplasm proteins; colonic neoplasms; cell differentiation; drug effect; pathology; tumor cells, cultured; physiology; rna; gene expression regulation; gene expression regulation, neoplastic; biosynthesis; cell culture; messenger rna; rna, messenger; colon tumor; tumor protein; carcinoma; cell adhesion; rna, neoplasm; colon; integrin; integrins; cell surface receptor; receptors, cell surface; interphase; hexamethylenebisacetamide; acetamides; humans; human; article; receptors, collagen; acetamide derivative; collagen receptor
Journal Title: Cell Growth & Differentiation
Volume: 3
Issue: 11
ISSN: 1044-9523
Publisher: American Association for Cancer Research  
Date Published: 1992-11-01
Start Page: 753
End Page: 762
Language: English
PUBMED: 1334691
PROVIDER: scopus
DOI/URL:
Notes: Article -- Export Date: 30 July 2019 -- Source: Scopus
Citation Impact
MSK Authors
  1. Sidney J Winawer
    276 Winawer
  2. Steven Huan-Ling Hsu
    4 Hsu
  3. Zhongfa Yan
    11 Yan