Study On The Structure And Function Of Human MT Gene Family And The TCP10L Preliminary Study On Gene Function

Although the precise mechanism of hepatocarcinogenesis resulted from environmental and inherited risk factors are different and largely unknown, considerable results revealed oxyradical and metal especially copper overload might be the important reason. Metallothioneins (MTs) are low molecular weight, cysteine-rich metal-binding proteins, involved in detoxification of heavy metals and antioxidant in vivo. Pervious works revealed that MT might have a role in cancer development. However, little information is available on the comparative analysis of expression of MT genes in vivo. In this study, we have characterized the members of MT family and analysis the expression profile of isoform-specific MT in hepatocellular carcinoma (HCC). We believe that there are 14 isoforms (MT-1A, -IB, -1C, -ID, -IE, -IF, -1G, -lg, -1H, -II, -1J, -IK, -1L, and -IX) subdivided into three classes of MT1 in MT family: MT-1C, -II may not encode mRNA; MT-1D, -1J and -1L may encode RNAs that are not functional in directing production of detectable MT proteins; others are functional genes. Thereinto, the MT-lg and MT-1K are reported at the first time as a functional gene. Their pattern of expression in different cells and tissues is unique and this may base on the regulatory element located on the promoter. There is a similar expression in the HCC specimen when compared with the corresponding para-neoplastic control liver tissue for MT-1E, MT-1F, and MT-1X. In contrast, the HCC specimens had decrease transcripts in MT-1A, MT-1G, MT-lg, MT-1H and MT-1K when compared with control specimens. Statistical data suggest a correlation between the occurrence of MT protein and tumor size of HCC. Metals were also quantified in specimens using the particle-induced X-ray emission method (PIXE). Results showed that accumulation of copper (Cu) in HCC, especially in small tumors, is greater than that in the surrounding liver parenchyma. The level of Cu present in small HCC has a negative relationship with the MT expression. We believe present work may help us to understand subdivision of functions of MT and to elucidate the mechanism of carcinogenesis of HCC.