The antitumor effect of TIG3 in liver cancer cells is involved in ERK1/2 inhibition
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Tazarotene-induced gene 3 (TIG3) was first characterized in tazarotene-treated human keratinocytes and identified as a retinoic acid responder gene, an important mediator of antitumor effects by retinoids. In this study, we aim to investigate the inhibitory effect of TIG3 on the growth of liver cancer and explore its underlying mechanism. Human hepatocellular carcinoma (HCC) Hep3B cells were transfected with plasmid GV141 carrying full-length TIG3 complementary DNA (cDNA). The effects of TIG3 on cell proliferation, apoptosis, and migration were determined in vitro. The suppressor effect of TIG3 on tumor growth was evaluated in vivo in a nude mouse HCC model. We observed that TIG3 expression is decreased in the Hep3B cell line as well as primary HCC tumors, and TIG3 expression inversely correlates with Ki-67 expression. Overexpression of TIG3 suppresses tumor growth in HCC both in vitro and in vivo via ERK1/2 inhibition by promoting apoptosis and inhibiting proliferation and migration. These findings identify TIG3 as an attractive therapeutic target for HCC.
KeywordsHepatocellular carcinoma TIG3 ERK Antitumor effect
This study was supported by grants funded by the Guangdong Natural Science Funds for Distinguished Young Scholar (S2013050014121), National Natural Science Foundation of China (81372634 and 81372633), and the Research Award Fund for Outstanding Young Teachers in Guangdong Provincial Higher Education Institutions (Yq2013133).
Compliance with ethical standards
Human/animal studies have been approved by The Institute of Medical Research Ethics Committee of Guangzhou Medical University. Written consent was obtained from each patient. All human studies were followed in accordance with the ethical standards laid down in 1964 Declaration of Helsinki and its amendments.
Conflicts of interest
- 27.Yip-Schneider MT, Klein PJ, Wentz SC, Zeni A, Menze A, Schmidt CM. Resistance to mitogen-activated protein kinase kinase (MEK) inhibitors correlates with up-regulation of the MEK/extracellular signal-regulated kinase pathway in hepatocellular carcinoma cells. J Pharmacol Exp Ther. 2009;329:1063–70.CrossRefPubMedGoogle Scholar
- 29.Davies BR, Logie A, McKay JS, Martin P, Steele S, Jenkins R, et al. Azd6244 (ARRY-142886), a potent inhibitor of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 kinases: mechanism of action in vivo, pharmacokinetic/pharmacodynamic relationship, and potential for combination in preclinical models. Mol Cancer Ther. 2007;6:2209–19.CrossRefPubMedGoogle Scholar