Carcinogenesis Advance Access originally published online on October 24, 2003
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Carcinogenesis, Vol. 25, No. 2, 241-248,
February 2004
© Oxford University Press; all rights reserved
CARCINOGENESIS |
Involvement of the PI 3-kinase signaling pathway in progression of colon adenocarcinoma
1 Mammalian Cell Genetics, Biotechnology Research Institute, National Research Council of Canada, 6100 Royalmount Avenue, Montreal, Quebec H4P 2R2, Canada and 2 Department of Medicine, McGill University, Montreal, Quebec H3A 1B1, Canada
The phosphoinositide 3-kinase (PI 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 up-regulated in colon cancers. In particular, the protein levels and phosphorylation status of Akt and p70 S6 kinase are up-regulated 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 the two subunits of PI 3-kinase, p85 and p110
, and PTEN were noted. Real-time quantitative PCR indicated an increase in levels of Akt message only, 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.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  L. Snoeks, C. R. Weber, J. R. Turner, M. Bhattacharyya, K. Wasland, and S. D. Savkovic Tumor Suppressor Foxo3a Is Involved in the Regulation of Lipopolysaccharide-Induced Interleukin-8 in Intestinal HT-29 Cells Infect. Immun., October 1, 2008; 76(10): 4677 - 4685. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. C. Manegold, C. Paringer, U. Kulka, K. Krimmel, M. E. Eichhorn, R. Wilkowski, K.-W. Jauch, M. Guba, and C. J. Bruns Antiangiogenic Therapy with Mammalian Target of Rapamycin Inhibitor RAD001 (Everolimus) Increases Radiosensitivity in Solid Cancer Clin. Cancer Res., February 1, 2008; 14(3): 892 - 900. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. M. Rhoads, B. A. Corl, R. Harrell, X. Niu, L. Gatlin, O. Phillips, A. Blikslager, A. Moeser, G. Wu, and J. Odle Intestinal ribosomal p70S6K signaling is increased in piglet rotavirus enteritis Am J Physiol Gastrointest Liver Physiol, March 1, 2007; 292(3): G913 - G922. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamaguchi, S.-H. Lee, J.-S. Kim, J. Wimalasena, S. Kitajima, and S. J. Baek Activating Transcription Factor 3 and Early Growth Response 1 Are the Novel Targets of LY294002 in a Phosphatidylinositol 3-Kinase-Independent Pathway Cancer Res., February 15, 2006; 66(4): 2376 - 2384. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Ju, J. Hong, J.-n. Zhou, Z. Pan, M. Bose, J. Liao, G.-y. Yang, Y. Y. Liu, Z. Hou, Y. Lin, et al. Inhibition of Intestinal Tumorigenesis in Apcmin/+ Mice by (-)-Epigallocatechin-3-Gallate, the Major Catechin in Green Tea Cancer Res., November 15, 2005; 65(22): 10623 - 10631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. J. Cohen, R. B. Cohen, and N. J. Meropol Targeting Signal Transduction Pathways in Colorectal Cancer--More Than Skin Deep J. Clin. Oncol., August 10, 2005; 23(23): 5374 - 5385. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wang, W. Ouyang, J. Li, L. Wei, Q. Ma, Z. Zhang, Q. Tong, J. He, and C. Huang Loss of Tumor Suppressor p53 Decreases PTEN Expression and Enhances Signaling Pathways Leading to Activation of Activator Protein 1 and Nuclear Factor {kappa}B Induced by UV Radiation Cancer Res., August 1, 2005; 65(15): 6601 - 6611. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Ikenoue, F. Kanai, Y. Hikiba, T. Obata, Y. Tanaka, J. Imamura, M. Ohta, A. Jazag, B. Guleng, K. Tateishi, et al. Functional Analysis of PIK3CA Gene Mutations in Human Colorectal Cancer Cancer Res., June 1, 2005; 65(11): 4562 - 4567. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. N. Kundranda, M. Henderson, K. J. Carter, L. Gorden, A. Binhazim, S. Ray, T. Baptiste, M. Shokrani, M. L. Leite-Browning, W. Jahnen-Dechent, et al. The Serum Glycoprotein Fetuin-A Promotes Lewis Lung Carcinoma Tumorigenesis via Adhesive-Dependent and Adhesive-Independent Mechanisms Cancer Res., January 15, 2005; 65(2): 499 - 506. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Yamaguchi, S.-H. Lee, T. E. Eling, and S. J. Baek Identification of Nonsteroidal Anti-inflammatory Drug-activated Gene (NAG-1) as a Novel Downstream Target of Phosphatidylinositol 3-Kinase/AKT/GSK-3{beta} Pathway J. Biol. Chem., November 26, 2004; 279(48): 49617 - 49623. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Moran, D. H. Hunt, S. H. Javid, M. Redston, A. M. Carothers, and M. M. Bertagnolli Apc Deficiency Is Associated with Increased Egfr Activity in the Intestinal Enterocytes and Adenomas of C57BL/6J-Min/+ Mice J. Biol. Chem., October 8, 2004; 279(41): 43261 - 43272. [Abstract] [Full Text] [PDF]
|
|