Neoplastic progression of human and rat intestinal cell lines after transfer of the ras and polyoma middle T oncogenes.
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.
Chastre
E
E
INSERM U55, Unité de Recherches sur les Peptides Neurodigestifs et le Diabète, Paris, France.
Empereur
S
S
Di Gioia
Y
Y
el Mahdani
N
N
Mareel
M
M
Vleminckx
K
K
Van Roy
F
F
Bex
V
V
Emami
S
S
Spandidos
D A
DA
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D003094:Collagen / Q000235:genetics; D015179:Colorectal Neoplasms / Q000209:etiology / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009857:Oncogenes; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; C029967:nidogen; D003094:Collagen