Carcinogenesis Advance Access published online on October 24, 2003
Carcinogenesis, doi:10.1093/carcin/bgg195
© 2003 by Oxford University Press
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CARCINOGENESIS
1 Mammalian Cell Genetics, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Ave., Montreal, Quebec H4P 2R2, Canada
* Corresponding author. E-mail: shi.shen{at}nrc.ca.
Received 30 November 2002
; revised 21 August 2003
; accepted 8 October 2003
The phosphoinositide 3-kinase signaling pathway has been shown to play a pivotal role in intracellular signal transduction pathways involved in cell growth, cellular transformation and tumorigenesis. Analysis of several colon adenocarcinoma cell lines indicates that the PI 3-kinase signaling pathway is upregulated in colon cancers. In particular, the protein levels and phosphorylation status of Akt and p70 S6 kinase are upregulated in colon adenocarcinoma cell lines. More significantly, we have demonstrated for the first time that the phosphorylation of FKHR, a downstream target of Akt, is increased in these cell lines. Intriguingly, phosphorylation of three components of the PI 3-kinase signaling pathway, namely Akt, p70 S6 kinase and FKHR, are in direct correlation with the degree of tumorigenic potential of the colon cell lines tested. No differences in the protein levels of both subunits of PI 3-kinase, p85 and p110
Involvement of the PI 3-kinase signaling pathway in progression of colon adenocarcinoma
2 Mammalian Cell Genetics, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Ave., Montreal, Quebec H4P 2R2, Canada; Department of Medicine, McGill University, Montreal, Quebec, H3A 1B1, Canada
, and PTEN were noted. Real-time quantitative PCR indicated only an increase in levels of Akt message, and not of the other signaling pathway components. Inhibition of the PI 3-kinase, with wortmannin, decreased the anchorage independent growth of colon cells in a soft agar assay. Hence the components of the PI 3-kinase signaling pathway could serve as potential candidates for drug development in treatment of colon cancer.
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