The TES gene at 7q31.1 is methylated in tumours and encodes a novel growth-suppressing LIM domain protein.
Many studies suggest that a multi-tissue tumour suppressor gene is located at human chromosome 7q31.1. We have cloned and characterized a novel gene at this locus. The TES gene lies within the minimal region of overlap of several LOH studies and appears to possess the properties of a tumour suppressor. TES is widely expressed and is predicted to encode a protein of 421 amino acids, with three C-terminal LIM domains. Mutation analysis of the coding TES exons in 21 human tumour-derived cell lines revealed the presence of a frameshift mutation in one allele in the breast cancer cell line ZR-75. Methylation of the CpG island at the 5' end of TES appears to be a remarkably frequent finding, occurring in seven out of 10 ovarian carcinomas and in each of the 30 tumour-derived cell lines tested. Moreover, forced expression of TES in HeLa or OVCAR5 cells, resulted in a profound reduction in growth potential, as determined by the colony formation assay. We believe that TES is a tumour suppressor gene that is inactivated primarily by transcriptional silencing resulting from CpG island methylation.
Tobias
E S
ES
Beatson Institute for Cancer Research, CRC Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Hurlstone
A F
AF
MacKenzie
E
E
McFarlane
R
R
Black
D M
DM
D001483:Base Sequence; D001943:Breast Neoplasms / Q000235:genetics; D002874:Chromosome Mapping; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics*; D018899:CpG Islands; D003598:Cytoskeletal Proteins; D019175:DNA Methylation; D005260:Female; D016368:Frameshift Mutation; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006367:HeLa Cells; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D060588:LIM Domain Proteins; D019656:Loss of Heterozygosity; D008297:Male; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics; D016601:RNA-Binding Proteins; D017422:Sequence Analysis, DNA; D014407:Tumor Cells, Cultured; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins; D001749:Urinary Bladder Neoplasms / Q000235:genetics
D003598:Cytoskeletal Proteins; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D016601:RNA-Binding Proteins; C429688:TES protein, human; D025521:Tumor Suppressor Proteins