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)
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| Spindel, E R; Sunday, M E; Hofler, H et al. (1987) Transient elevation of messenger RNA encoding gastrin-releasing peptide, a putative pulmonary growth factor in human fetal lung. J Clin Invest 80:1172-9 |
| Spindel, E R; Zilberberg, M D; Habener, J F et al. (1986) Two prohormones for gastrin-releasing peptide are encoded by two mRNAs differing by 19 nucleotides. Proc Natl Acad Sci U S A 83:19-23 |
