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.
[...] Read more.
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 (AS
2O
3) 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, whereas
MT3-knockdown in TSGH-8301 cells had the opposite effect. The experiments indicated that
MT3 is an arsenic- and hypoxia-upregulated oncogene that promotes cell growth and invasion of bladder carcinoma cells via downregulation of
NDRG1,
NDRG2, and
MASPIN expressions.
Full article