Abstract
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.
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Acknowledgements
We would like to thank Prof N Lemoine (ICRF, London) for the pancreatic tumour cell lines and Prof R Brown (Medical Oncology, University of Glasgow) for the ovarian tumours and cell lines used in this study. This work has been supported by a programme grant from The Cancer Research Campaign (CRC) of the United Kingdom. Accession number GenBank accession no. AJ250865
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Tobias, E., Hurlstone, A., MacKenzie, E. et al. The TES gene at 7q31.1 is methylated in tumours and encodes a novel growth-suppressing LIM domain protein. Oncogene 20, 2844–2853 (2001). https://doi.org/10.1038/sj.onc.1204433
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DOI: https://doi.org/10.1038/sj.onc.1204433
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