Project: Research project

    Project Details


    Bombesin-like peptides, a family of peptides originally isolated from frog
    skin, are found throughout mammalian brain and gastrointestinal tract where
    they serve as neuroregulatory peptides. Bombesin occurs in large amounts
    in small cell carcinoma of the lung (SCCL) in which it is produced
    ectopically or as part of the neoplastic process. Bombesin is a potent
    releasor of gastrointestinal hormones and in the brain influences body
    temperature and blood sugar regulation. The objective of this proposal is
    to characterize human bombesins so as to determine their amino acid
    sequences in the major organ systems in which they occur. By knowing which
    bombesin sequences occur in which organs, the physiologic roles and
    potential of bombesin as a disease or tumor marker can then be evaluated. Human bombesin sequences will be deduced from the base sequences of
    complementary DNA (cDNA) made from mRNA from a pulmonary carcinoid tumor
    rich in bombesin. Preliminary studies have already shown that this tumor
    has high levels of two different mRNAs that encode precursors of
    bombesin-like peptides. Peptides corresponding to the bombesin sequences
    will be synthesized, antisera prepared, and radioimmunoassays established.
    Lung biopsy specimens and blood samples from patients with SCCL will then
    be screened to determine if tumor bombesin can be a clinically useful tumor
    marker. Neonatal lung, gastrointestinal and brain tissue will be obtained
    from human surgical and postmortem specimens and examined for bombesin
    mRNAs differing from tumor bombesin mRNA. The sequences of such mRNAs will
    be determined and any new bombesin-like peptides will be synthesized and
    antisera prepared. Levels of bombesin-like peptides and mRNAs will then be
    quantitated in stomach, duodenal, and colonic surgical or biopsy samples of
    tissue found to be normal and in tissue from individuals with peptic ulcer
    disease and other GI disorders. Antisera and cDNA probes will be given to
    collaborators for immunohistochemical and in situ histo-hybridization
    distribution studies. To investigate additional bombesin-like peptides, a
    ranatensin-encoding cDNA will be prepared from mRNA from frog skin and used
    to identify related sequences in human tissue. As time permits the gene(s)
    encoding bombesin-like peptides will be investigated. (1)
    Effective start/end date8/1/841/31/99


    • National Institutes of Health


    • Medicine(all)


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