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.
Imperial Cancer Research Fund Medical Oncology Unit, Western General Hospital, Edinburgh, United Kingdom.
L M
LM
Gilmour
K G
KG
Macleod
A
A
McCaig
W J
WJ
Gullick
J F
JF
Smyth
S P
SP
Langdon
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