# INHIBITION OF IN VITRO TRANSFORMATION BY RETINOIDS

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 1988 · $143,050

## Abstract

It is proposed to continue our studies of the mechanisms whereby retinoids
can inhibit carcinogen induced neoplastic transformation.  Using model in
vitro systems in which chemical and physical carcinogens induce neplastic
change and in which retinoids are active in preventing that change, we
propose to conduct following investigations.  These studies are directed
towards answering two major questions which are limiting the development of
retinoids as effective cancer preventive agents in the clinic:  1) how to
retinoids work at the cellular and biochemical level; 2) can the potential
for retinoids to act as tumor promoters be avoided?  Based on previously
funded work and on recent developments on cellular control mechanisms, we
hypothesize that retinoids act by modulating cellular
phosphorylation/dephosphorylation reactions and propose a series of
experiments to test this hypothesis.  At the biological level, cultures
will be treated with known modulators of protein phosphorylation and their
effects alone and in conjunction with retinoids on the neoplastic
transformation of cells monitored.  At the biochemical level the
phosphorylation state of cellular proteins will be monitored.  In addition
we will conduct extensive studies of phosphorylation of recently described
residual proteins, possibly associated with the cytoskeleton, and of the
composition and phosphorylation of H1 histones.  Altered phosphorylation of
both these substrates could induce the pleiotropic effects of retinoids.
Phamacological studies will also be conducted to determine if the tumor
promoting activity of retinoic acid can be explained by its inhibitory
effects on intracellular communication and if this effect can be avoided by
the use of retinol-like compounds which do not possess this property.
These studies should aid in the rationale development of cancer
chemoprevention strategies.

## Key facts

- **NIH application ID:** 3179354
- **Project number:** 5R01CA039947-04
- **Recipient organization:** UNIVERSITY OF HAWAII AT MANOA
- **SAM.gov UEI:** NSCKLFSSABF2
- **Principal Investigator:** JOHN S BERTRAM
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $143,050
- **Award type:** 5
- **Project period:** 1984-09-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179354

## Citation

> US National Institutes of Health, RePORTER application 3179354, INHIBITION OF IN VITRO TRANSFORMATION BY RETINOIDS (5R01CA039947-04). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179354. Licensed CC0.

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