Open AccessNotch1 activation contributes to tumor cell growth and proliferation in human hepatocellular carcinoma HepG2 and SMMC7721 cells
Author(s) -
Juan Gao,
Yun Dong,
Bicheng Zhang,
Yimin Xiong,
Weitian Xu,
Yi C,
Meng Dai,
Yu Zhao,
Hualin Xu,
Zheng Guo
Publication year - 2012
Publication title -
international journal of oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.405
H-Index - 122
ISSN - 1019-6439
DOI - 10.3892/ijo.2012.1606
Subject(s) - cell growth , cell cycle , cancer research , notch signaling pathway , carcinogenesis , biology , cell , tumor progression , oncogene , apoptosis , signal transduction , microbiology and biotechnology , cancer , biochemistry , genetics
Notch signaling controls cellular differentiation and proliferation. Recentstudies have shown that Notch signaling plays an important role in the carcinogenesisand progression of a growing number of malignant tumors. We investigated the effectof Notch1 activation on human hepatocellular carcinoma (HCC). In five human HCCcell lines, it was found that SMMC7721 had relatively high while HepG2 relativelylow expression of Notch1 and the activity of Notch signaling. Notch1 activationby transfection of active intracellular region of Notch1 (ICN1) into HCC HepG2cells enhanced cell growth and proliferation, including in vitro single cell colonyformation, anchorage-independent proliferation, and in vivo tumorigenicity. Notch1activation also promoted HepG2 cell cycle progression. Suppression of Notch1 activationby RNAi of Notch1 or by γ-secretase inhibitor (GSI) in HCC SMMC7721 cells decreasedcell growth capability and blocked cell cycle progression. Moreover, it was foundthat suppression of Notch1 activation induced SMMC7721 cell apoptosis, as demonstratedby apoptosis assays. These findings indicate that Notch1 activation promotes humanHCC cell growth and proliferation, which may contribute to the progression ofthis type of malignant carcinoma.