Abstract
Tumor necrosis factor receptor (TNFR) associated factor 4 (TRAF4) was initially identified as a gene amplified and overexpressed in breast carcinomas. Our aim was to evaluate whether TRAF4 protein overexpression exists in other cancer types. Immunohistochemistry analysis of tumor samples from 623 patients with 20 different tumor types showed that TRAF4 was overexpressed in 268 tumors (43%), including 82 of 137 lung adenocarcinomas (60%). Interestingly, 32 primary tumors and their matching metastases exhibited mostly similar TRAF4 expression pattern. TRAF4 protein overexpression was limited to cancer cells and the subcellular localization was consistently cytoplasmic in a large majority of cases. To investigate changes in TRAF4 gene copy number, 125 cases from six different types of carcinomas were also analysed by fluorescence in situ hybridization. Out of the 28 cases (22%) showing an increased TRAF4 gene copy number, 23 (82%) were overexpressing the protein. Thus, TRAF4 gene amplification is one of the mechanisms responsible for TRAF4 protein overexpression in human cancers. Considering that TRAF4 is located at 17q11.2 in a region of amplification devoid of known oncogenes and is commonly overexpressed in cancer, our data support an oncogenic role for TRAF4.
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Acknowledgements
We thank DJ Heard for critical reading of the manuscript, C Tomasetto for helpful discussions, F Devez and V Ducruit for expert technical assistance. The BAC clone RP11-386F9 was kindly provided by M Rocchi. This work was supported by funds from the Institut National de la Santé et de la Recherche Médicale, the Association pour la Recherche sur le Cancer (CH Régnier, contract no. 4801) and the Alliance des Recherches sur le Cancer.
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Camilleri-Broët, S., Cremer, I., Marmey, B. et al. TRAF4 overexpression is a common characteristic of human carcinomas. Oncogene 26, 142–147 (2007). https://doi.org/10.1038/sj.onc.1209762
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DOI: https://doi.org/10.1038/sj.onc.1209762
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