Journal Article

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 R. Roberts, Haojie Huang and Long Yu

in Carcinogenesis

Volume 33, issue 12, pages 2568-2577
Published in print December 2012 | ISSN: 0143-3334
Published online September 2012 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgs287
Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas

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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.

Journal Article.  5744 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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