# INTERACTIONS OF TUMOR PROMOTERS WITH RECEPTORS

> **NIH NIH R01** · PURDUE UNIVERSITY · 1988 · $138,326

## Abstract

The molecular mechanism of action of the tumor promoting phorbol esters
will be investigated by determining the normal physiological function of
the phorbol ester receptor protein in cells and the effect of tumor
promoters on receptor function.  Phorbol esters elicit numerous changes in
cellular morphology, growth, and differentiation.  This is generally
assumed to occur via binding reversibly and with high affinity and
specificity to a cellular receptor protein which has protein kinase
activity tightly associated with it.  Both membrane bound and soluble
cytosolic receptors exist in cells although the latter requires calcium and
phospholipid to function.  This and other data suggest that as part of its
normal function in cells the soluble cytosolic receptor becomes associated
with cell membranes and that phorbol esters may directly affect this aspect
of its function.  The research plan involves analysis of changes in the
localization of the receptor in stimulated cells by quantitation of phorbol
ester binding activity, ultraviolet light microscopic observation of cells
stained with fluorecently labeled receptor specific antibodies, and viewing
of cells stained with receptor specific antibodies covalently bound to
ferritin using a trasmission electron microscope.  The antibodies will be
produced by the monoclonal hybridoma method using as antigen receptor
protein purified from mouse brain.  Initial biochemical experiments will
use as a model system primary mouse spleen cells stimulated with lectins,
phorbol esters, and lymphokines.  These results will be applied to a study
of primary mouse epidermal keratinocytes and C3H 10T-1/2 fibroblasts in
which growth and morphological controls are affected by calcium,
polypeptide growth factors, and phorbol esters.  Ultimately the
investigation will be extended to mouse epidermis, in vivo, so that the
effects of in vivo treatments known to affect the carcinogenic process in
epidermis can be compared to the results obtained with cells in culture.
These studies as well as a biochemical investigation of interactions of the
receptor with other cellular proteins will lead to the development of a
cell free system in which the actions of phorbol esters can be observed.
These studies will help characterize the biological action of phorbol
esters and aid in understanding the biological processes of tumor promotion
and chemical carcinogenesis.

## Key facts

- **NIH application ID:** 3173801
- **Project number:** 5R01CA036262-05
- **Recipient organization:** PURDUE UNIVERSITY
- **SAM.gov UEI:** YRXVL4JYCEF5
- **Principal Investigator:** CURTIS L. ASHENDEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1988
- **Award amount:** $138,326
- **Award type:** 5
- **Project period:** 1984-01-01 → 1989-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173801

## Citation

> US National Institutes of Health, RePORTER application 3173801, INTERACTIONS OF TUMOR PROMOTERS WITH RECEPTORS (5R01CA036262-05). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173801. Licensed CC0.

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