# INHIBITION OF IN VITRO TRANSFORMATION BY RETINOIDS

> **NIH NIH R01** · UNIVERSITY OF HAWAII AT MANOA · 1991 · $214,343

## Abstract

The induction of neoplastic transformation by chemical and physical
carcinogens are be modeled in in vitro culture systems.  In one of the
most widely used system, the IOTI/2 assay system, the frequency of
transformation can be enhanced by tumor promoters such as TPA, and
inhibited by retinoids.  This applicant seeks to continue studies into
the mechanism of action of retinoids in inhibiting the carcinogenic
process.  Although retinoids are being widely used clinically, their
mechanisms of action is not understood.  We have recently shown that
retinoids strongly induce gap junctional cell communication between
normal or between neoplastic cells.  This is associated with enhanced
growth control of these cells.  We propose that growth regulatory signals
are transmitted via gap junctions.  We have identified the major
structural protein in 10T1/2 cells as connexin43 and find that retinoids
increase cellular levels of this protein, as measured on Western blots
and the message for this protein determined by Northern blotting.  In
contrast to retinoid effects on homologous communication, communication
between normal and transformed cells is inhibited by retinoids.  We
propose to examine the role of retinoids in controlling the assembly of
connexins into functional junctions in normal and neoplastic cells and
the role of protein phosphorylation in junctional conductance.
Modification of connexin phosphorylation by agents which up regulate
(cAMP), or down regulate (TPA) communication will be examined.  To
determine the validity of this model system to the cancer chemopreventive
action of retinoids in humans, we propose to examine retinoid effects on
gap junctional communication in an in vitro human skin system.
Communication will be measured by dye injection and electrochemical
means.  Induction of junctional complexes will be probed by
immunofluorescence and electron microscopy.  Retinoid effects in
pre-neoplastic human skin cells will also be studied.  These studies will
aid our understanding of growth control processes in general, their
aberration in neoplasia, and the mechanism of action of chemopreventive
agents which are in extensive clinical use.

## Key facts

- **NIH application ID:** 3179351
- **Project number:** 2R01CA039947-06A2
- **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:** 1991
- **Award amount:** $214,343
- **Award type:** 2
- **Project period:** 1984-09-01 → 1994-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3179351

## Citation

> US National Institutes of Health, RePORTER application 3179351, INHIBITION OF IN VITRO TRANSFORMATION BY RETINOIDS (2R01CA039947-06A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3179351. Licensed CC0.

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