Downregulation of Metallothionein 1F, a putative oncosuppressor, by loss of heterozygosity in colon cancer tissue

Downregulation 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. Integral analysis of microarray data with loss...

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Published in:Biochimica et biophysica acta 2012-06, Vol.1822 (6), p.918-926
Main Authors: Yan, Dong-Wang, Fan, Jun-Wei, Yu, Zhen-hai, Li, Ming-xue, Wen, Yu-Gang, Li, Da-Wei, Zhou, Chong-Zhi, Wang, Xiao-Liang, Wang, Quan, Tang, Hua-Mei, Peng, Zhi-Hai
Format: Article
Language:English
Subjects:
Aged
Aged, 80 and over
Animals
Apoptosis
Cell Adhesion
Cell Line, Tumor
Cell Movement
Colon carcinogenesis
Colonic Neoplasms - genetics
Colonic Neoplasms - metabolism
Colonic Neoplasms - pathology
CpG Islands
DNA Methylation
Down-Regulation
Epigenetics
Female
Gene Expression Regulation, Neoplastic
Genes, Tumor Suppressor
Humans
Loss of Heterozygosity
Male
Metallothionein
Metallothionein - biosynthesis
Metallothionein - genetics
Metallothionein - metabolism
Mice
Mice, Nude
Microarray
Middle Aged
Neoplasm Invasiveness
Promoter Regions, Genetic
Sequence Analysis, DNA
Transplantation, Heterologous
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Summary:Downregulation 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. Integral 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. MT1F, MT1G, MT1X, and MT2A gene expression was significantly downregulated in colon cancer tissue (p
ISSN:0925-4439
0006-3002
1879-260X
DOI:10.1016/j.bbadis.2012.02.021