| Literature DB >> 21575863 |
Emilie A Bard-Chapeau1, Shuangwei Li, Jin Ding, Sharon S Zhang, Helen H Zhu, Frederic Princen, Diane D Fang, Tao Han, Beatrice Bailly-Maitre, Valeria Poli, Nissi M Varki, Hongyang Wang, Gen-Sheng Feng.
Abstract
The human 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.Entities:
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Year: 2011 PMID： 21575863 PMCID： PMC3098128 DOI： 10.1016/j.ccr.2011.03.023
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743