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Overexpression of the Tpl-2/Cot oncogene in human breast cancer

Abstract

Tpl-2/Cot proto-oncogene encodes a serine threonine kinase and was initially cloned as a provirus insertion site in MoMuLV-induced T cell lymphomas in rats. Tpl-2 locus was also shown to be affected by provirus insertion in MMTV-induced mammary carcinomas in mice. The involvement of Tpl-2 in 35 human breast paired tumour specimens versus their corresponding adjacent normal tissue was evaluated. Tpl-2 was found overexpressed in 14 of the 35 breast tumours tested using a semi-quantitative RT – PCR method. Gene amplification was detected in eight out of the 14 specimens overexpressing Tpl-2, suggesting the increased number of copies of Tpl-2 gene as a possible mechanism for Tpl-2 overexpression. Significant association was found between the overexpression of Tpl-2 and stage I of the tumours, indicating that this molecular alteration may be an early event in the development of the disease. Furthermore, overexpression of Tpl-2 was associated with positive progesterone receptor status of the samples. This is the first report on the Tpl-2 oncogene linked to human breast tumours suggesting that it may be a key molecule for the study of human breast cancer.

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Acknowledgements

We would like to thank Professor Philip N Tsichlis for stimulating discussions.

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Sourvinos, G., Tsatsanis, C. & Spandidos, D. Overexpression of the Tpl-2/Cot oncogene in human breast cancer. Oncogene 18, 4968–4973 (1999). https://doi.org/10.1038/sj.onc.1202891

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