Author/Authors :
Bard-Chapeau، نويسنده , , Emilie A. and Li، نويسنده , , Shuangwei and Ding، نويسنده , , Jin and Zhang، نويسنده , , Sharon S. and Zhu، نويسنده , , Helen H. and Princen، نويسنده , , Frederic and Fang، نويسنده , , Diane D. and Han، نويسنده , , Tao and Bailly-Maitre، نويسنده , , Beatrice and Poli، نويسنده , , Valeria and Varki، نويسنده , , Nissi M. and Wang، نويسنده , , Hongyang and Feng، نويسنده , , Gen-Sheng، نويسنده ,
Abstract :
Summary
man gene Ptpn11, which encodes the tyrosine phosphatase Shp2, may act as a proto-oncogene because dominantly activating mutations have been detected in several types of leukemia. Herein we report a tumor-suppressor function of Shp2. Hepatocyte-specific deletion of Shp2 promotes inflammatory signaling through the Stat3 pathway and hepatic inflammation/necrosis, resulting in regenerative hyperplasia and development of tumors in aged mice. Furthermore, Shp2 ablation dramatically enhanced diethylnitrosamine (DEN)-induced hepatocellular carcinoma (HCC) development, which was abolished by concurrent deletion of Shp2 and Stat3 in hepatocytes. Decreased Shp2 expression was detected in a subfraction of human HCC specimens. Thus, in contrast to the leukemogenic effect of dominant-active mutants, Ptpn11/Shp2 has a tumor-suppressor function in liver.
