Expression of tumor necrosis factor alpha converting enzyme in endocrine cancers.
Tumor necrosis factor alpha converting enzyme (TACE) mediates shedding of human epidermal growth factor receptor-4 (HER4). Recent data suggest that released HER4 intracellular domain (4ICD) induces apoptosis in breast cancer. TACE expression, as measured by immunohistochemical analysis, was observed in 183 of 383 breast carcinomas, 39 of 217 ovarian carcinomas, and 16 of 24 and 17 of 24 hormonesensitive and hormone-insensitive prostate carcinomas, respectively. HER4 expression was detected in breast carcinomas by using 2 antibodies recognizing an extracellular or intracellular epitope. TACE expression was predominantly seen in tumors with high levels of 4ICD and membranous HER4. Apoptotic activity was measured by the terminal deoxynucleotidyl transferase-mediated nick-end labeling (TUNEL) assay and cleaved caspase-3 staining 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 herein show TACE expression in endocrine cancers and further support a role for TACE in breast cancer apoptosis.
Kirkegaard
Tove
T
Endocrine Cancer Research Group, Division of Cancer Sciences and Molecular Pathology, University Department of Surgery, Glasgow Royal Infirmary, Glasgow, Scotland.
Naresh
Anjali
A
Sabine
Vicky S
VS
Tovey
Sian M
SM
Edwards
Joanne
J
Dunne
Barbara
B
Cooke
Timothy G
TG
Jones
Frank E
FE
Bartlett
John M S
JM
D051722:ADAM Proteins / Q000096:biosynthesis*; D000072198:ADAM17 Protein; D017209:Apoptosis / Q000502:physiology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000473:pathology; D004701:Endocrine Gland Neoplasms / Q000201:enzymology* / Q000473:pathology; D066246:ErbB Receptors / Q000096:biosynthesis; D005260:Female; D015870:Gene Expression; D006801:Humans; D020287:In Situ Nick-End Labeling; D008297:Male; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000473:pathology; D066247:Receptor, ErbB-4; D011960:Receptors, Estrogen / Q000096:biosynthesis
D011960:Receptors, Estrogen; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4; D051722:ADAM Proteins; D000072198:ADAM17 Protein; C000606462:ADAM17 protein, human