| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 1904993 | Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease | 2012 | 9 Pages |
PurposeDownregulation of metallothionein (MT) genes has been reported in several tumors with discrepant results. This study is to investigate molecular mechanism of MT gene regulation in colon cancer which is characterized by tumor suppressor gene alterations.Experimental designIntegral analysis of microarray data with loss of heterozygosity (LOH) information was employed. Quantitative real-time PCR and immunohistochemistry were used to validate MT isoform expression in colon cancer tissues and cell lines. The effects of MT1F expression on RKO cell survival and tumorigenesis was analyzed. Bisulphite sequencing PCR (BSP) and methylation-specific PCR were employed to detect the methylation status of the MT1F gene in colon cancer tissues and cell lines. DNA sequencing was used to examine the LOH at the MT1F locus.ResultsMT1F, MT1G, MT1X, and MT2A gene expression was significantly downregulated in colon cancer tissue (p < 0.05). Exogenous MT1F expression increased RKO cell apoptosis and inhibited RKO cell migration, invasion and adhesion as well as in vivo tumorigenicity. Downregulation of MT1F gene in majority of human colon tumor tissues is mainly through mechanism by loss of heterozygosity (p = 0.001) while CpG island methylation of MT1F gene promoter region was only observed in poorly differentiated, MSI-positive RKO and LoVo colon cancer cell lines.ConclusionsMT1F is a putative tumor suppressor gene in colon carcinogenesis that is downregulated mainly by LOH in colon cancer tissue. Further studies are required to elucidate a possible role for MT1F downregulation in colon cancer initiation and/or progression.
► The expression of MT1F, MT1G, MT1X, and MT2A was downregulated in colon cancer tissue. ► MT protein expression was negatively associated with tumor status. ► Exogenous MT1F expression increased RKO cell apoptosis. ► Exogenous MT1F expression inhibited in vivo tumorigenicity. ► Loss of heterozygosity is the main reason for MT1F mRNA downregulation in colon cancer tissues.
