Neoplastic progression of human and rat intestinal cell lines after transfer of the ras and polyoma middle T oncogenes

Gastroenterology. 1993 Dec;105(6):1776-89. doi: 10.1016/0016-5085(93)91076-t.


Background: Activation of the p21ras and pp60c-src oncoproteins occurred at high incidence in the early stage of human colorectal carcinogenesis. Our study aimed to investigate the role of these signal-transduction pathways in the process of initiation and promotion of the malignant phenotype in intestinal cells.

Methods: The human Ha-ras and the polyoma middle T (Py-MT) viral oncogenes were transferred into large T oncogene of simian virus 40 immortalized rat intestinal epithelial SLC-44 cells and human colonic adenocarcinoma Caco-2 cells.

Results: These transfers conferred the tumorigenic and invasive phenotypes on immortalized SLC-44 cells and potentiated the tumorigenicity of Caco-2 cells and markedly repressed the terminal differentiation of this cell line. In SLC-44T cells, induction of the invasive phenotype by the activated Ha-ras oncogene correlated with weak expression of E-cadherin and reduced accumulation of the transcripts encoding the basement membrane components alpha 1 (IV) collagen, nidogen, and BM40, which might result partly from the inactivation of the transforming growth factor beta signaling pathway. The down-regulation of the alpha 1 (IV) collagen messenger RNA in SLC-44T cells was not due to the protein kinase C-dependent pathways or the secretion of autocrine factor(s).

Conclusions: These results suggest that the activation of the p21ras and Py-MT/pp60c-src oncogenic pathways are critical effectors at different stages of colorectal carcinogenesis and in Caco-2 cells interferes with the program of enterocyte differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics*
  • Base Sequence
  • Cell Differentiation
  • Cell Line
  • Cell Transformation, Neoplastic / genetics*
  • Collagen / genetics
  • Colorectal Neoplasms / etiology
  • Colorectal Neoplasms / genetics*
  • Genes, ras*
  • Humans
  • Membrane Glycoproteins / genetics
  • Mice
  • Mice, Nude
  • Molecular Sequence Data
  • Oncogenes*
  • RNA, Messenger / analysis
  • Rats
  • Transfection*


  • Antigens, Polyomavirus Transforming
  • Membrane Glycoproteins
  • RNA, Messenger
  • nidogen
  • Collagen