# ROLE OF ARACHIDONATE METABOLITES IN TUMOR PROMOTION

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1991 · $172,586

## Abstract

Anti-inflammatory agents are potent inhibitors of phorbol ester tumor
promotion in mouse skin; this ha been interpreted as demonstrating a
requirement for inflammation in promotion.  We hypothesize that it is the
dermal inflammation produced by tumor promoters, and other irritants, via
arachidonate release that is responsible for the hyperplasia of the
overlying epidermis and that chronic inflammation, regardless of whether it
is caused by a chemical or physical agent, is sufficient and necessary to
cause both sustained hyperplasia and promotion of tumors in initiated skin.
In order to test our hypotheses we wish to do the following: (1) Determine
whether arachidonic acid release induced by phorbol esters (TPA) is via
protein kinase C (PKC) or represents a PKC-independent signalling mechanism
that is common to all promoters, including the nonPKC types.  We propose
that the principle function of PKC may be signal amplification, allowing
TPA to activate phospholipase A2 at lower doses. (2) Demonstrate that
inflammation, whether caused by physical or chemical agents, causes
hyperplasia of the overlying epidermis and that eicosanoids are the
principal mediators of this proces.  Both physical (abrasion of the inner
ear and injury of underside of skin) and chemical (dinitrofluorobenzene and
topical application of arachidonic acid and select irritants) means will be
used to achieve inflammation.  In order to show that this inflammation is
required for hyperplasia, inhibitors of eicosanoid synthesis) will also be
used. In vivo treatment for various times coupled with in vitro expression
of hyperplasia in organ culture will also be used a measure of the
requirement for nonepidermal factors (inflammation) for hyperplasia. (3)
Determine whether repeated stimuli of the above agents results in sustained
hyperplasia and where this can be demonstrated, whether promotion of tumors
in initiated skin will occur. (4) Determine if a paracrine mechanism exists
such that the eicosanoids produced by the differentiated epidermal cells
have their effect on the basal cells, which synthesize little eicosanoid.
Specifically, receptor affinity and number for prostaglandin E2, F2alpha
and D2 will be compared between populations of keratinocytes separated on
the basis of differentiation.  The second messenger or signal transduction
pathway to which each of the PG receptors is coupled will also be
determined.

## Key facts

- **NIH application ID:** 3172129
- **Project number:** 5R01CA034443-08
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** SUSAN M FISCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $172,586
- **Award type:** 5
- **Project period:** 1984-07-01 → 1995-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172129

## Citation

> US National Institutes of Health, RePORTER application 3172129, ROLE OF ARACHIDONATE METABOLITES IN TUMOR PROMOTION (5R01CA034443-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172129. Licensed CC0.

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