# RETINOIC ACID--ROLE IN DIFFERENTIATION AND CARCINOGENES

> **NIH NIH R01** · DANA-FARBER CANCER INST · 1987 · $94,292

## Abstract

Mouse teratocarcinoma (TC) stem cells are pluripotent cells which are
similar in some respects to the cells of the inner cell mass of the mouse
embryo.  The teratocarcinoma stem cells are tumorigenic; these TC stem
cells exhibit malignant properties such as progressive growth and
transplantability.  However, after treatment with low (less than 10 to
the-6 concentrations of retinoic acid (RA), these TC stem cells are induced
to differentiate into nonmalignant differentiated cell types such as
fibroblasts or parietal endoderm cells.  This proposal addresses the
question of how retinoic acid converts the tumorigenic TC stem cells into
benign differentiated cells with limited growth potential.  Although the
mechanism by which RA causes differentiation is not understood, it is clear
from our previous work (PNAS 80:  5880-5884) and the work of others that RA
can regulate gene expression.  In this grant, we propose to use molecular
biological, and biochemical techniques to isolated specific TC cell genes
which are rapidly induced by RA during the differentiation process.  We
will employ both the F9 and P19 TC stem cell lines for the isolation of
these "early" RA-inducible genes.  We then plan to use the cDNA clones for
these genes which are expressed at very early times, (1-6 hrs.) after RA
addition to determine whether RA directly regulates these genes at the
level of transcription, to determine whether dibutyryl cyclic AMP regulates
these genes at the transcriptional level, to assay for the proteins encoded
by these genes, and to determine if the expression of these "early"
RA-inducible genes in transient or stable.  We will determine if a
functional cellular RA binding protein is required for expression of these
"early" RA-inducible genes.  We will also examined the expression of these
"early" RA-inducible genes in several different teratocarinoma lines.
Further characterization of these RA-inducible genes will include the
isolation of genomic clones, in order to determine the sequences of these
genes, including the conding, noncoding, and flanking sequences.  Since
retinoic acid can profoundly influence developmental processes in vivo, and
RA inhibits carcinogenesis in several experimental systems, the studies
outlined in this proposal will provide important and relevant information
concerning the mechanism by which RA causes differentiation in this
experimental system.  The studies in this grant proposal will also lead to
future studies in which we will determine whether expression of these
genes, (without RA addition, under control of a different promotor
sequence), will promote differentiation and loss of tumorigenicity.

## Key facts

- **NIH application ID:** 3177689
- **Project number:** 5R01CA039036-03
- **Recipient organization:** DANA-FARBER CANCER INST
- **SAM.gov UEI:** DPMGH9MG1X67
- **Principal Investigator:** LORRAINE J GUDAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1987
- **Award amount:** $94,292
- **Award type:** 5
- **Project period:** 1985-02-01 → 1988-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177689

## Citation

> US National Institutes of Health, RePORTER application 3177689, RETINOIC ACID--ROLE IN DIFFERENTIATION AND CARCINOGENES (5R01CA039036-03). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177689. Licensed CC0.

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