BRS-3: a novel bombesin receptor subtype selectively expressed in testis and lung carcinoma cells.
The bombesin (BN)-like peptides mediate a diverse spectrum of biological activities and have been implicated as autocrine growth factors in the pathogenesis and progression of some human small cell lung carcinoma tumors. Previously, two mammalian BN-like peptide receptor subtypes, gastrin-releasing peptide receptor and neuromedin-B receptor, have been cloned and characterized. In this study, we have isolated and characterized human genomic and complementary DNA (cDNA) clones encoding a new BN-like peptide receptor subtype, BN receptor subtype 3 (BRS-3). Expression of BRS-3 cDNA in Xenopus oocytes encodes a functional receptor that is specifically activated by BN-like peptides. Chromosome mapping studies indicate that the BRS-3 gene is located on human chromosome X. BRS-3 mRNA expression in rat tissues is limited to secondary spermatocytes in testis. In contrast, BRS-3 mRNA is widely expressed in a panel of human cell lines from all histological types of lung carcinoma. These results suggest a role for BN-like peptides and their receptors in mammalian reproductive physiology and also indicate that BRS-3 could serve as a potential therapeutic target for human lung carcinoma.
Department of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
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Fathi
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Corjay
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Shapira
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Wada
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Benya
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Jensen
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Viallet
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Sausville
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Battey
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D001839:Bombesin / Q000378:metabolism*; D002874:Chromosome Mapping; D003001:Cloning, Molecular; D004247:DNA; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism*; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D013094:Spermatozoa / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014960:X Chromosome; D014981:Xenopus
D012333:RNA, Messenger; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D004247:DNA; D001839:Bombesin