Ptpn11/Shp2 Acts as a Tumor Suppressor in Hepatocellular Carcinogenesis

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• 作者：Emilie  ; A. Bard-Chapeau¹ ; ² ; ⁵ ; ⁶ ; Shuangwei Li¹ ; ⁵ ; Jin Ding³ ; Sharon  ; S. Zhang¹ ; Helen  ; H. Zhu¹ ; Frederic Princen² ; Diane  ; D. Fang¹ ; Tao Han³ ; Beatrice Bailly-Maitre² ; ⁷ ; Valeria Poli⁴ ; Nissi  ; M. Varki¹ ; Hongyang Wang³ ; Gen-Sheng Feng¹ ; ³ ; ^{gfeng@ucsd.edu"" rel=""nofollow}
• 刊名：Cancer Cell
• 出版年：2011
• 出版时间：17 May 2011
• 年：2011
• 卷：19
• 期：5
• 页码：629-639
• 全文大小：2417 K

文摘

Summary

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.