Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas

Jun Mao, Hongxiu Yu, Chenji Wang, Luhong Sun, Wei Jiang, Pingzhao Zhang, Qianyi Xiao, Dingbing Han, Hexige Saiyin, Jingde Zhu, Taoyang Chen, Lewis Rowland Roberts, Haojie Huang, Long Yu

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Members of the metallothionein (MT) family are short, cysteine-rich proteins involved in metal metabolism and detoxification, suggesting that MT proteins protect cells from damage caused by electrophilic carcinogens and thereby constitute a critical surveillance system against carcinogenesis. However, the roles of MT proteins in human hepatocellular carcinoma (HCC) are not fully understood. We identified a member of the MT family, termed MT1M. MT1M is expressed in various normal tissues with the highest level in the liver. MT1M expression can be induced by heavy metals and protect Escherichia coli from heavy metal toxicity. However, MT1M expression markedly decreased in human HCC specimens. A methylation profiling analysis indicated that the MT1M promoter is methylated in the majority of HCC tumors examined. Moreover, restored expression of MT1M in the HCC cell line Hep3B, which lacks endogenous MT1M expression, suppressed cell growth in vitro and in vivo and augmented apoptosis induced by tumor necrosis factor α. Furthermore, stable expression of MT1M in Hep3B cells blocked tumor necrosis factor α-induced degradation of IκBα and transactivation of NF-κB. We conclude that MT1M is a novel member of the MT family. Frequent downregulation of MT1M in human HCC may contribute to liver tumorigenesis by increasing cellular NF-κB activity.

Original languageEnglish (US)
Article numberbgs287
Pages (from-to)2568-2577
Number of pages10
JournalCarcinogenesis
Volume33
Issue number12
DOIs
StatePublished - Dec 2012

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Metallothionein
Hepatocellular Carcinoma
Neoplasms
Carcinogenesis
Tumor Necrosis Factor-alpha
Proteins
Liver
Heavy Metals
Carcinogens
Methylation
Transcriptional Activation
Cysteine
Down-Regulation
Metals
Apoptosis
Escherichia coli
Cell Line
Growth

ASJC Scopus subject areas

  • Cancer Research

Cite this

Mao, J., Yu, H., Wang, C., Sun, L., Jiang, W., Zhang, P., ... Yu, L. (2012). Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas. Carcinogenesis, 33(12), 2568-2577. [bgs287]. https://doi.org/10.1093/carcin/bgs287

Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas. / Mao, Jun; Yu, Hongxiu; Wang, Chenji; Sun, Luhong; Jiang, Wei; Zhang, Pingzhao; Xiao, Qianyi; Han, Dingbing; Saiyin, Hexige; Zhu, Jingde; Chen, Taoyang; Roberts, Lewis Rowland; Huang, Haojie; Yu, Long.

In: Carcinogenesis, Vol. 33, No. 12, bgs287, 12.2012, p. 2568-2577.

Research output: Contribution to journalArticle

Mao, J, Yu, H, Wang, C, Sun, L, Jiang, W, Zhang, P, Xiao, Q, Han, D, Saiyin, H, Zhu, J, Chen, T, Roberts, LR, Huang, H & Yu, L 2012, 'Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas', Carcinogenesis, vol. 33, no. 12, bgs287, pp. 2568-2577. https://doi.org/10.1093/carcin/bgs287
Mao J, Yu H, Wang C, Sun L, Jiang W, Zhang P et al. Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas. Carcinogenesis. 2012 Dec;33(12):2568-2577. bgs287. https://doi.org/10.1093/carcin/bgs287
Mao, Jun ; Yu, Hongxiu ; Wang, Chenji ; Sun, Luhong ; Jiang, Wei ; Zhang, Pingzhao ; Xiao, Qianyi ; Han, Dingbing ; Saiyin, Hexige ; Zhu, Jingde ; Chen, Taoyang ; Roberts, Lewis Rowland ; Huang, Haojie ; Yu, Long. / Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas. In: Carcinogenesis. 2012 ; Vol. 33, No. 12. pp. 2568-2577.
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