It has been previously reported that p110γ-deficient mice have defective T lymphocytic and neutrophil function. Now, Sasaki et al. demonstrate that p110γ, the phosphatidylinositol 3-kinase (PI3K) isoform activated by G protein-coupled receptors (GPCR), may have a role in inhibiting the progression of colon cancer. p110γ-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 p110γ 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 p110γ led to reduced colony growth in vitro and to reduced tumor growth in vivo, indicating that the kinase activity of p110γ 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 p110γ 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)Kγ. Nature 406: 897-902. [Online Journal]