Expression of erbB-4/HER-4 growth factor receptor isoforms in ovarian cancer.
Immunohistochemical expression of erbB4 protein was identified in 93% (49 of 53) of ovarian cancers using the HFR-1 antibody (targeted to the cytoplasmic domain of the erbB4 receptor) and in 89% (47 of 53) of ovarian cancers using the H4.77.16 antibody (targeted to the extracellular domain). Tumors of serous histology were more likely to express a higher level of erbB4 than endometrioid tumors, and for stage III serous tumors, long-term survival was associated with moderate to high coexpression of erbB4 and erbB2. Within ovarian cancer cell lines, high erbB4 expression was associated with cisplatin resistance. Using reverse transcription-PCR, the presence of multiple isoforms of erbB4 mRNA was identified in both ovarian primary tumors and cell lines. Splice variants in the juxtamembrane (JM-a and JM-d) and cytoplasmic (CT-a and CT-b) regions were identified in mRNA of both cell lines and primary tumors. The use of an anti-erbB4 blocking antibody suggested that erbB4 was not the mediator of the growth stimulatory effects of neuregulin in ovarian cancer cells and indeed could potentially antagonize this effect.
Gilmour
L M
LM
Imperial Cancer Research Fund Medical Oncology Unit, Western General Hospital, Edinburgh, United Kingdom.
Macleod
K G
KG
McCaig
A
A
Gullick
W J
WJ
Smyth
J F
JF
Langdon
S P
SP
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D017398:Alternative Splicing; D000906:Antibodies / Q000494:pharmacology; D001483:Base Sequence; D015153:Blotting, Western; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D018284:Cystadenocarcinoma, Serous / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D020890:Neuregulin-1 / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020033:Protein Isoforms; D066247:Receptor, ErbB-4; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014407:Tumor Cells, Cultured
D000906:Antibodies; D020890:Neuregulin-1; D020033:Protein Isoforms; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4