# CA2+-DEPENDENT PROCESSES--PHORBOL ESTER TUMOR PROMOTION

> **NIH NIH R01** · UNIVERSITY OF WISCONSIN-MADISON · 1993 · $141,600

## Abstract

We continue to test the hypothesis that the activation of PKC (a major TPA
receptor) is an initial event in tumor promotion and ODC-gene transcription
by the tumor promoter TPA.  Thus, the continuing goals of this project are
two-fold:

1. To determine the role of PKC in tumor promotion by TPA.  Specifically,
we plan:  a) To determine the tumor promoting activity of diacylglycerols
(DG) which activate PKC.  We reported that, under the conditions where TPA
is a complete tumor promoter, DG is a stage II tumor promoter.  We will
investigate the mechanism underlying differences between the tumor
promoting activities of TPA and DG.  b) To determine whether differences in
tumor promoting susceptibility of B2S (sensitive) and B2R (resistant)
strains of mice are due to differential translocation and down-regulation
of PKC isozymes by TPA.  c) To directly demonstrate the role of PKC in
tumor promotion by TPA, we plan to use C3H10T1/2 cell line.  We will
transfect these cells with PKC gene expression vectors and determine
whether different PKC isozyme overproducing cells are more sensitive to
tumor promotion by TPA than their parental cells.

2. To determine the role of PKC in TPA-induced ODC gene transcription.  We
plan to: a) Transfect T24 cells with PKC gene expression vector and clone
PKC overproducing transfectants to directly demonstrate the role of PKC in
ODC gene expression.  b) Analyze the mechanism of enhanced ODC gene
transcription by TPA.  In this study, we will use the 5'-flanking region of
ODC gene to determine TPA-responsive enhancer elements, isolate trans-
acting factors (proteins) and determine whether the trans-acting factors
are substrates for PKC which may increase in vitro transcription of ODC
gene.  c) Analyze the relation of PKC down regulation to superinduction of
ODC activity after repeated TPA applications to mouse skin.

This study will permit an evaluation of the role of PKC in ODC gene
transcription and tumor promotion by TPA.

## Key facts

- **NIH application ID:** 3172960
- **Project number:** 5R01CA035368-10
- **Recipient organization:** UNIVERSITY OF WISCONSIN-MADISON
- **SAM.gov UEI:** LCLSJAGTNZQ7
- **Principal Investigator:** AJIT K VERMA
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $141,600
- **Award type:** 5
- **Project period:** 1983-07-01 → 1995-02-28

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172960

## Citation

> US National Institutes of Health, RePORTER application 3172960, CA2+-DEPENDENT PROCESSES--PHORBOL ESTER TUMOR PROMOTION (5R01CA035368-10). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172960. Licensed CC0.

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