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HINT1 inhibits β-catenin/TCF4, USF2 and NFκB activity in human hepatoma cells

✍ Scribed by Lin Wang; Haiyang Li; Yujing Zhang; Regina M. Santella; I. Bernard Weinstein

Publisher
John Wiley and Sons
Year
2009
Tongue
French
Weight
425 KB
Volume
124
Category
Article
ISSN
0020-7136

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✦ Synopsis

Abstract

In this study we explored the relevance of Hint, a novel tumor suppressor gene, to human hepatoma. The human hepatoma cell lines Hep3B and HepG2 express very low levels of the HINT1 protein but the Huh7 cells express a relatively high level. In Hep3B and HepG2 cells, but not in Huh7 cells, the promoter region of Hint1 is partially methylated and treatment with 5‐azadcdeoxycytidine increased expression of the HINT1 protein and Hint1 mRNA in Hep3B and HepG2 cells. Increased expression of HINT1 in HepG2 cells markedly inhibited their growth. It also inhibited the transcriptional activities of β‐catenin/TCF4, and USF2, and inhibited the expression of endogenous cyclin D1 and TGFβ2. Furthermore, HINT1 co‐immunoprecipitated with USF2 in extracts of Hep2 cells. HINT1 also inhibited NFκB transcription factor reporter activity and inhibited translocation of the endogenous p65 protein to the nucleus of HepG2 cells. Therefore, decreased expression of the Hint1 gene through epigenetic silencing may play a role in enhancing the growth of a subset of human hepatoma by increasing the expression of genes controlled by the transcription factors β‐catenin, USF2, and NFκB. © 2008 Wiley‐Liss, Inc.

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