Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.


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

EDITORS' CHOICE

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).


To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882