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.