Two erbB-4 transcripts are expressed in normal breast and in most breast cancers.
ErbB-4 is a recently described member of the epidermal growth factor receptor (EGFR) family which together with erbB-3 acts as a receptor for a group of ligands known as the neuregulins (NRGs) or heregulins (HRGs). Unlike the EGFR and erbB-2 relatively little is known about the expression of erbB-4 in human tumours. Using RT-PCR and Southern blotting analysis we have investigated the expression of erbB-4 mRNA in a range of human tumour cell lines and in normal and malignant breast tissue. Using primers which amplified a 658 base pair (bp) region corresponding to part of the cytoplasmic domain of c-erbB-4 we found the receptor was expressed in some but not all breast and ovarian tumour cell lines and also in a glioma cell line. The highest level of erbB-4 expression was found in the ovarian carcinoma OVCAR-3 and the breast carcinoma T-47D. In all cell lines where the 'full-length' erbB-4 was detected, a second previously undescribed c-erbB-4 sequence was also found as a 610 bp PCR product. The alternative PCR product was identical in sequence to c-erbB-4 except for a deletion of 48 bp which encodes a consensus phosphatidylinositol 3-kinase (PI3K) binding site. This suggested that the two forms of erbB-4 might interact with different intracellular signalling pathways and therefore influence a wider variety of cellular responses to heregulin than previously thought. Expression of both erbB-4 variants was found in 7/7 normal breast tissues but only in 9/12 breast tumours analysed. In line with the terminology of Elenius et al. (1997b) we have designated the two isoforms of the C-terminal transcripts as CT-a (full-length) and CT-b which lacks the P13K binding motif. These results identify suitable cell lines for the further investigation of erbB-4 expression and function and suggest that the role of erbB-4 in breast cancer warrants further investigation with larger numbers of normal and malignant breast tissues.
Sawyer
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Section of Immunology, Institute of Cancer Research, Sutton, Surrey, UK.
Hiles
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Page
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Crompton
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Dean
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D017398:Alternative Splicing; D000595:Amino Acid Sequence; D001483:Base Sequence; D001665:Binding Sites; D001940:Breast / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism*; D066246:ErbB Receptors / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D006801:Humans; D015345:Oligonucleotide Probes; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D016133:Polymerase Chain Reaction; D066247:Receptor, ErbB-4; D012016:Reference Values; D017384:Sequence Deletion; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
D015345:Oligonucleotide Probes; D019869:Phosphatidylinositol 3-Kinases; C587689:ERBB4 protein, human; D066246:ErbB Receptors; D066247:Receptor, ErbB-4