Expression of Tumor Necrosis Factor α Converting Enzyme in Endocrine Cancers

Tove Kirkegaard, Anjali Naresh, Vicky S. Sabine, Sian M. Tovey, Joanne Edwards, Barbara Dunne, Timothy G. Cooke, Frank E. Jones, John M.S. Bartlett
2008 American Journal of Clinical Pathology  
Tumor necrosis factor-_ converting enzyme (TACE) mediates shedding of human epidermalgrowth factor receptor-4 (HER4). Recent data suggests that released HER4 intracellulardomain (4ICD) induces apoptosis in breast cancer.TACE expression, as measured by immunohistochemistry, was observed in 183/383 breast carcinomas, 39/217 ovarian carcinomas, and 16/24 and 17/24 hormone-sensitive and hormone insensitive prostate carcinomas, respectively. HER4 expression was detected in breast carcinomas, using
more » ... carcinomas, using two antibodies recognizing an extracellular or intracellular epitope.TACE expression was predominantly seen in tumors with high levels of 4ICD and membrane HER4. Apoptotic activity was measured by TUNEL assay and cleaved caspase-3staining in breast carcinomas. There was no significant association between cleaved caspase-3 or TUNEL positivity and 4ICD, whereas TUNEL positivity was seen predominantly in tumors with high levels of internalized HER4. The data presented here show TACE expression in endocrine cancers and further supports a role for TACE in breast cancer apoptosis.
doi:10.1309/n6yb6ydvf58ycnhn pmid:18426733 fatcat:ked6kqopijaxdjxohzu53u6bay