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

International Journal of Molecular Sciences
Ke-Hung TsuiHorng-Heng Juang

Abstract

Metallothioneins have been viewed as modulators in a number of biological regulations regarding cancerous development; however, the function of metallothionein 3 (MT3) 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 MT3 levels than RT-4, HT1376, and T24 cells. Immunoblot and RT-qPCR assays showed that arsenic (AS₂O₃) treatments enhanced the gene expression of MT3. Hypoxia induced HIF-1α, HIF-2α, and MT3 expression; furthermore, HIF-2α-knockdown attenuated hypoxic activation on MT3 expression. Ectopic overexpression of MT3 increased cell proliferation, invasion, and tumorigenesis significantly in T24 and HT1376 cells in vitro and in vivo; however, MT3-knockdown in TSGH-8301 cells had the reverse effect. Moreover, knockdown of MT3 enhanced arsenic-induced apoptosis determined by the Annexin V-FITC apoptosis assay. MT3-overexpression downregulated the gene expressions of N-myc downstream regulated gene 1 (NDRG1), N-myc downstream regulated gene 2 (NDRG2), and the mammary serine protease inhibitor (MASPIN) in HT1376 and T24 cells, w...Continue Reading

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Citations

Jan 12, 2021·Molecular Therapy. Methods & Clinical Development·Emanuele BurattiAndrea Dardis
Apr 16, 2021·Molecular Biology Reports·Ardeshir Afshar Mazandaran, Parvin Khodarahmi
Jun 17, 2021·Neoplasia : an International Journal for Oncology Research·Myung-Chul KimYongbaek Kim
May 18, 2019·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Peng SunDong Zhang

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Methods Mentioned

BETA
xenografts
xenograft
flow cytometry
FCS
PCR
Assay
Transfection

Software Mentioned

SigmaStat
it
PAX

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