Metallothionein MT1M is a tumor suppressor of human hepatocellular carcinomas
Menée in vitro et in vivo, cette étude suggère qu'une protéine de la famille des métallothionéines, MT1M, joue un rôle de suppresseur de tumeurs dans les carcinomes hépatocellulaires
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 metallothionein 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 (TNF-α). Furthermore, stable expression of MT1M in Hep3B cells blocked TNF-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.
http://carcin.oxfordjournals.org/content/early/2012/09/12/carcin.bgs287.abstract