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Sci. STKE, 29 August 2000
Vol. 2000, Issue 47, p. tw4
[DOI: 10.1126/stke.2000.47.tw4]


Tumor Suppression PI3K{gamma} Inhibits Colorectal Tumor Progression

It has been previously reported that p110{gamma}-deficient mice have defective T lymphocytic and neutrophil function. Now, Sasaki et al. demonstrate that p110{gamma}, the phosphatidylinositol 3-kinase (PI3K) isoform activated by G protein-coupled receptors (GPCR), may have a role in inhibiting the progression of colon cancer. p110{gamma}-deficient mice developed colorectal tumors and had adenomatous proliferation that correlated with increased levels of Bcl-2, cyclin D1, cdk2, and cdk4. The expression of p110{gamma} protein was not detected in colon cancer cell lines and was reduced in most samples of human colon adenocarcinomas. Overexpression of wild-type and catalytically inactive p110{gamma} led to reduced colony growth in vitro and to reduced tumor growth in vivo, indicating that the kinase activity of p110{gamma} may not be important in regulating epithelial colon cell proliferation. The authors speculate that because Gα i2-deficient mice also develop colon carcinomas, this suggests that p110{gamma} and Gαi2 interact with a GPCR that regulates colon cell proliferation and tumor growth.

Sasaki, T., Irie-Sasaki, J., Horie, Y., Bachmaier, K., Fata, J.E., Li, M., Suzuki, A., Bouchard, D., Ho, A., Redston, M., Gallinger, S., Khokha, R., Mak, T.W., Hawkins, P.T., Stephens, L., Scherer, S.W., Tsao, M., and Penninger, J.M. (2000) Colorectal carcinomas in mice lacking the catalytic subunit of PI(3)K{gamma}. Nature 406: 897-902. [Online Journal]

Citation: PI3K{gamma} Inhibits Colorectal Tumor Progression. Sci. STKE 2000, tw4 (2000).

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