BOMBESIN-LIKE PEPTIDES: STRUCTURE AND PHYSIOLOGY

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)