Metallothionein 3 Is a Hypoxia-Upregulated Oncogene Enhancing Cell Invasion and Tumorigenesis in Human Bladder Carcinoma Cells

• Published in: International journal of molecular sciences 2019-02, Vol.20 (4), p.980
• Main Authors: Tsui, Ke-Hung, Hou, Chen-Pang, Chang, Kang-Shuo, Lin, Yu-Hsiang, Feng, Tsui-Hsia, Chen, Chiu-Chun, Shin, Yi-Syuan, Juang, Horng-Heng
• Format: Article
• Language: English
• Subjects: Adenocarcinoma; Apoptosis; bladder; Bladder cancer; Breast; Breast cancer; Cell growth; Cell proliferation; Colon; Colon cancer; Deoxyribonucleic acid; DNA; Gene expression; Hepatocellular carcinoma; Hypoxia; Liver; Mammals; MASPIN; Metallothionein; metallothionein 3; Molecular weight; mRNA; Nasopharynx; NDRG1; Oncogenes; Oxidative stress; Prostate; Proteins; Thyroid; Toxicity; Tumorigenesis; Tumors; Urinary bladder; Xenografts; Xenotransplantation
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms20040980

Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 ( ) in bladder cancer is unexplored. We determined the regulatory mechanisms and potential function of MT3 in bladder carcinoma cells. Real-Time Reverse Transcriptase-Polymerase Chain Reaction (RT-qPCR) assays revealed that TSGH-8301 cells expressed more levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS₂O₃) treatments enhanced the gene expression of . Hypoxia induced , , and expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on expression. Ectopic overexpression of increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, -knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. -overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 ( ), N-myc downstream regulated gene 2 ( ), and the mammary serine protease inhibitor ( ) in HT1376 and T24 cells, whereas -knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of , , and expressions.