Authors:
Wenbin Xiao, Hong Hong, Yuko Kawakami, Yuko Kato, Dianqing Wu, Hiroki Yasudo, Akiko Kimura, Hiromi Kubagawa, Luigi F. Bertoli, Randall S. Davis, Luan A. Chau, Joaquin Madrenas, Cyrus C. Hsia, Anargyros Xenocostas, Thomas J. Kipps, Lothar Hennighausen, Atsushi Iwama, Hiromitsu Nakauchi, and Toshiaki Kawakami
Summary:
Given its catalytic activity to generate diacylglycerol and inositol 1,4,5-trisphosphate, phospholipase C (PLC) is implicated in promoting cell growth. However, we found that PLC-β3-deficient mice develop myeloproliferative disease, lymphoma, and other tumors. The mutant mice have increased numbers of hematopoietic stem cells with increased proliferative, survival, and myeloid-differentiative abilities. These properties are dependent on Stat5 and can be antagonized by the protein phosphatase SHP-1. Stat5-dependent cooperative transformation by active c-Myc and PLC-β3 deficiency was suggested in mouse lymphomas in PLC-β3−/− and in Eμ-myc;PLC-β3+/− mice and human Burkitt's lymphoma cells. The same mechanism for malignant transformation seems to be operative in other human lymphoid and myeloid malignancies. Thus, PLC-β3 is likely a tumor suppressor.
Source:
Cancer Cell; Vol. 16, Issue 2, 161-171 (08/04/09)