# DNA REARRANGEMENTS AND THE C-MYC ONCOGENE

> **NIH NIH R01** · PRINCETON UNIVERSITY · 1993 · $215,841

## Abstract

DESCRIPTION (Adapted from applicant's abstract):  DNA rearrangements that
alter the myc family of proto-oncogenes have been more frequently linked to
human and mouse cancers than any oncogene except ras.  Chromosomal
translocation, retrovirus insertion and gene amplification lead to
deregulated or elevated expression of the myc protein and complex changes
in cellular growth properties.  Yet the mechanism by which deregulated myc
expression disrupts cell growth remains unknown.  The goal of this proposal
is to determine how DNA rearrangements disrupt myc gene expression, and how
deregulated expression contributes to the transformation of mouse lymphoid
cells and causes plasmacytomas.

The first goal of this project will be to determine the mechanism of c-myc
mRNA turnover.  An important feature of c-myc gene regulation is the very
short half-life of the mRNA (less than 30 min).  Chromosomal translocations
usually displace the first exon of c-myc and induce mRNA stabilization.
The cis-acting determinants of RNA turnover and the basic mechanism by
which c-myc mRNA is degraded will be investigated.  A related goal will be
to determine the cis-acting determinants that mediate the differential
regulation of c-myc and granulocyte-macrophages-CSF mRNA stability.

The second goal of this project is to identify the secondary mutations that
cause B cell lymphomas in a unique mouse transgenic model in which an
immunoglobulin enhancer-linked N-myc transgene induces tumors with long
latency (greater than one year).  Retrovirus infection of these mice
potentiates rapid (four mo) B cell lymphomas, suggesting that the
retrovirus integration site will identify the secondary genetic lesions
that collaborate with myc.  The pathology of tumor progression will also be
investigated to better understand the role that individual mutations play
in the disease.

The third goal of the project will be to understand the molecular basis of
the c-myc promoter suppression in tumor cells.  Specifically, the c-myc
gene will be studied for suppression after microinjection into mouse
embryos, or transfer of the extended chromosomal domain into cells by YAC
cloning.  Proper gene regulation may be dependent on either distant
flanking sequences or developmental factors that are not reproduced in
cultured cells.  DNA rearrangements may primarily act by overriding the
normal suppression of the c-myc gene so an understanding of the basic
mechanism of gene suppression is critical to understanding malignant
transformation.

## Key facts

- **NIH application ID:** 3177947
- **Project number:** 5R01CA039192-10
- **Recipient organization:** PRINCETON UNIVERSITY
- **SAM.gov UEI:** NJ1YPQXQG7U5
- **Principal Investigator:** MICHAEL David COLE
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $215,841
- **Award type:** 5
- **Project period:** 1984-07-01 → 1996-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177947

## Citation

> US National Institutes of Health, RePORTER application 3177947, DNA REARRANGEMENTS AND THE C-MYC ONCOGENE (5R01CA039192-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177947. Licensed CC0.

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