Gamma-heregulin: a fusion gene of DOC-4 and neuregulin-1 derived from a chromosome translocation.
gamma-Heregulin was identified as an isoform resulting from alternate splicing of the neuregulin-1 gene, after cloning of its cDNA from the MDA-MB-175 breast cancer cell line. gamma-Heregulin was shown to promote growth of cultured MDA-MB-175 cells resulting from activation of its cognate ErbB tyrosine kinase reporters. We show here that gamma-heregulin is transcribed from a fusion gene resulting from a chromosome translocation in MDA-MB-175 cells. The fusion chromosome is described as dic(8:11)(8qter-->8p12::11q13-->11pter). As a result, the 5' end of the gamma-heregulin gene is derived from the stress-induced gene, DOC-4 (11q13), while the 3' end is from the neuregulin-1 gene (8p12). Thus, expression of gamma-heregulin is under the control of the DOC-4 promoter. By contrast with MDA-MB-175 cells, RT-PCR failed to detect a gamma-heregulin transcript in either E9.5 to E13.5 embryonic mouse tissues, adult mouse tissues or other human tumour cell lines. We conclude, therefore, that gamma-heregulin is not a native isoform of the neuregulin-1 gene, but a novel growth factor that may contribute to tumour cell proliferation.
Liu
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X
Victor Chang Cardiac Research Institute, Darlinghurst, NSW, Australia.
Baker
E
E
Eyre
H J
HJ
Sutherland
G R
GR
Zhou
M
M
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D002898:Chromosomes, Human, Pair 8; D003001:Cloning, Molecular; D017931:DNA Primers; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D020890:Neuregulin-1 / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D017931:DNA Primers; D020890:Neuregulin-1; D011993:Recombinant Fusion Proteins; C108697:gamma-heregulin