# RETINOIC ACID--ROLE IN DIFFERENTIATION AND CARCINOGENES

> **NIH NIH R01** · COLUMBIA UNIV NEW YORK MORNINGSIDE · 1991 · $95,222

## Abstract

Retinoids, a class of compounds comprising natural and synthetic
analogs of retinol (vitamin A), have been identified as inhibitors
of malignant transformation.  Retinoids are thought to inhibit
carcinogenesis through their profound effects on cell
differentiation and cell proliferation, but the mechanism(s) by
which retinoids regulate these processes are not understood. The
aims of this grant were to characterize the earliest actions of
retinoic acid (RA) in the F9 murine teratocarcinoma stem cell line,
which differentiates into endoderm, a type of epithelial cell, in
the presence of RA.  We have now identified at least two genes,
ERA-1 (Early Retinoic Acid-1) and ERA-2, which are expressed
rapidly (within 2 hr.) after RA addition.  The increases in the
ERA-1 and ERA-2 mRNAs in response to RA are insensitive to protein
synthesis inhibitors, but are prevented by RNA synthesis inhibitors
(eg. actinomycin D) suggesting that the ERA-1 and ERA-2 mRNAs may
represent a primary, direct response to RA.  We've demonstrated by
nuclear transcriptional run-off assays that the ERA-1 gene is
regulated by RA at the level of transcription, and we also have
preliminary evidence that the half-life of ERA-1 mRNA doesn't
change upon RA addition.  To our knowledge, this is the first
discovery of such rapid regulation of genes by RA in any
differentiation system.  Therefore, analysis of these ERA genes
should provide much new information about the mechanism of RA
action.

We propose to identify additional genes which exhibit rapid mRNA
induction in response to RA.  We also propose to sequence the ERA-
1, and ERA-2 genes, to determine their genomic structures,
including their 5' flanking regions, and to delineate the DNA
sequences and nuclear proteins required for their transcriptional
regulation by RA.  We want to produce antibodies specific for the
ERA-1, and ERA-2 gene products as we now have data which suggests
that the ERA-1 gene product is a DNA binding protein.  To analyze
the functions of their gene products, these ERA genes, under the
control of a heterologous promoter (in the sense, and antisense
orientations), will be transfected into F9 stem cells, and these
transfected lines will be assessed for their ability to
differentiate.  These studies should result in major advances in
the understanding of RA action in differentiation, the regulation
of cell proliferation, and the inhibition of malignant
transformation.

## Key facts

- **NIH application ID:** 3177694
- **Project number:** 7R01CA039036-08
- **Recipient organization:** COLUMBIA UNIV NEW YORK MORNINGSIDE
- **SAM.gov UEI:** F4N1QNPB95M4
- **Principal Investigator:** LORRAINE J GUDAS
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $95,222
- **Award type:** 7
- **Project period:** 1988-07-01 → 1993-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3177694

## Citation

> US National Institutes of Health, RePORTER application 3177694, RETINOIC ACID--ROLE IN DIFFERENTIATION AND CARCINOGENES (7R01CA039036-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3177694. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*