# BOMBESIN-LIKE PEPTIDES: STRUCTURE & PHYSIOLOGY

> **NIH NIH R01** · OREGON REGIONAL PRIMATE RESEARCH CENTER · 1990 · $140,909

## Abstract

Gastrin-releasing peptide (GRP) and neuromedin B (NMB) are the
mammalian homologues of the amphibian bombesin-like peptides
bombesin and ranatensin, respectively.  These two peptides are
widely distributed in neurons; but, of greatest clinical
importance, GRP occurs commonly in small cell carcinoma of the lung
(SCCL) and medullary carcinoma of the thyroid (MCT) and has  been
shown to be a growth factor for normal and neoplastic pulmonary
cells.  In neuroendocrine cells of normal adult lung and thyroid,
GRP is expressed at low, barely detectable levels.  By contrast,
in fetal lung and thyroid, and in neoplastic lung and thyroid (MCT
and SCCL) GRP gene expression is greatly enhanced.  The mechanisms
responsible for GRP gene activation in neoplasia and normal
development are unknown.  Even less is known about NMB gene
expression although NMB has growth factor activity similar to GRP,
though at 1/10 the potency.  During the prior grant period (NIRA)
I reported the cloning of the gene and mRNAs which encode human
GRP (hGRP) and demonstrated that the GRP gene is activated in human
fetal lung and fetal thyroid.  My objective in this proposal are
(1) to analyze the regulation of GRP gene transcription in SCCL
and MCT cell lines and (2) to initiate studies in the analysis of
the NMB gene.

Specifically we propose to study the following elements of GRP gene
transcription:  (A) Determine whether the differences in GRP mRNA
concentration in different cell lines are caused by changes in GRP
gene transcription, (B) Determine the cis-acting elements in the
hGRP 5'-flanking region necessary for tissue-specific expression
in MCT and SCCL cell lines and to identify putative enhancer and
repressor elements, and (C) Determine if certain hormones and
growth factors can regulate GRP gene expression in MCT and SCCL
cell lines.  Gene transcription will be measured by nuclear run-on
assay.  Regulatory sequences in the 5'-flanking region will be
identified by transient expression of hGRP gene/reporter gene
constructs (eg., chloramphenicol acetyl transferase, CAT).

We will use our recently cloned cDNAs encoding human NMB to: (A)
Characterize the tissue-specific expression of the NMB gene by RNA
blot analysis and in situ hybridization.  (B) Analyze and then
compare the human NMB gene to the human GRP gene and determine the
chromosomal localization of the NMB gene and (C) Use the NMB cDNA
to probe at low stringency for related genes.

## Key facts

- **NIH application ID:** 3178049
- **Project number:** 5R01CA039237-06
- **Recipient organization:** OREGON REGIONAL PRIMATE RESEARCH CENTER
- **Principal Investigator:** ELIOT R SPINDEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $140,909
- **Award type:** 5
- **Project period:** 1987-08-01 → 1993-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3178049

## Citation

> US National Institutes of Health, RePORTER application 3178049, BOMBESIN-LIKE PEPTIDES: STRUCTURE & PHYSIOLOGY (5R01CA039237-06). Retrieved via MORVS 2026-10-24 from https://api.morvs.ai/grant/nih/3178049. Licensed CC0.

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