Send to

Choose Destination
Gastroenterology. 1993 Dec;105(6):1776-89.

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

Author information

INSERM U55, Unité de Recherches sur les Peptides Neurodigestifs et le Diabète, Paris, France.



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.


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.


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).


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.

[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center