# REGULATION OF GROWTH AND DIFFERENTIATION BY RETINOIDS

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 1988 · $172,587

## Abstract

The objective of this proposal is to understand the molecular
mechanism(s) through which retinoic acid (RA), cAMP and laminin
interact to control the growth and differentiation of F9
teratocarcinoma cells.  RA inhibits the expression of the proto-
oncogene c-myc in F9 stem cells.  We will determine the
mechanism(s) for this regulation.  We will also investigate the
function of c-myc in F9 growth and differentiation by
transfecting stem cells with a retrovirus containing an expressible
c-myc gene.  Thus we will determine whether continued high
expression of c-myc can prevent the effects of RA and cAMP on
growth and differentiation.  F9 cells grown on either gelatin or
laminin-coated dishes can be induced to differentiate into parietal
endoderm-like cells by cholera toxin + 1-methyl, 3-
isobutylxanthine (CT/MIX) in the absence of RA.  Laminin
potentiates the differentiation of this cAMP-induced pathway.
Thus we will characterize this cAMP-induced pathway by
determining whether it leads to irreversible differentiation,
regulates differentiation-specific genes at the transcriptional
level and by exploring the relationship between the RA and cAMP
pathways through the isolation of RA and cAMP resistant
mutants.  We will also study the mechanism by which laminin
potentiates the cAMP-induced differentiation pathway.  We will
establish the kinetic properties of the laminin enhanced cAMP-
induced differentiation pathway.  Subsequently, we will determine
if the effects of laminin are mediated through specific cell
surface receptors, and whether the interaction of laminin with its
receptor increases cAMP-dependent protein kinase.  Through the
use of butyrate, we will determine whether the failure of previous
investigators to detect the cAMP-induced pathway was due to the
metabolism of dibutyryl cAMP to butyrate which in turn blocked
the cAMP pathway.  Retinoids are being used experimentally to
manage some malignancies.  However rational approaches to use
of retinoids and cAMP elevating agents requires an understanding
of the molecular mechanisms by which these compounds interact.
The studies outlined in this proposal will provide new insights into
these mechanisms.

## Key facts

- **NIH application ID:** 3170422
- **Project number:** 2R01CA032543-06A1
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **SAM.gov UEI:** FBYMGMHW4X95
- **Principal Investigator:** Richard M. Niles
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $172,587
- **Award type:** 2
- **Project period:** 1982-08-01 → 1991-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170422

## Citation

> US National Institutes of Health, RePORTER application 3170422, REGULATION OF GROWTH AND DIFFERENTIATION BY RETINOIDS (2R01CA032543-06A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170422. Licensed CC0.

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