Objective: Human cervical cancer oncogene (HCCR)-1, previously identified in cervical cancer and its cell lines, has been reported to play an important role in tumor progression in several cancers as a suppressor of apoptosis. However, the role of in the tumorigenesis of stomach cancer has not been identified. This study examined the role of as a suppressor of apoptosis during tumorigenesis in gastric cancer, along with its possible regulatory pathway.
Methods: We employed several techniques including western blotting, semiquantitative reverse transcription polymerase chain reaction, diphenyltetrazolium bromide assay, chromatin immunoprecipitation assay, fluorescence-activated cell sorting, and knockdown with short hairpin RNA to elucidate the role of .
Results: We observed that hepatocyte growth factor (HGF) upregulated expression. In addition, the expression levels of β-catenin, T cell factor-1 (TCF1), and B-cell lymphoma 2 () were increased, whereas that of tumor protein 53 () was decreased following HGF treatment. knockdown in NUGC-3 and MKN-28 cells decreased the expression of TCF1 and phosphorylated β-catenin and increased the binding activity on the binding site of the promoter. This identifies the possible involvement of the Wnt/β-catenin pathway in HGF-induced regulation. We also confirmed the role of in HGF-induced anti-apoptotic activity. p53 protein expression was increased, whereas that of bcl2 was decreased with HGF treatment in knockdown cells, while the apoptotic activity was increased.
Conclusion: Our study suggests the anti-apoptotic activity of HGF-induced expression and that HGF may regulate HCCR-1 via TCF1/β-catenin in stomach cancer.
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Int J Biol Sci
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Faculty of Health Sciences, University of Macau, Taipa, Macau.
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Department of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan.
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Department of Geriatric Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 211166, P. R. China.
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School of Pharmacy and Life Sciences, Robert Gordon University, Aberdeen, UK.
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