# CARCINOGEN-VIRAL ONCOGENE INTERACTIONS IN MAMMARY CANCER

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 1990 · $200,349

## Abstract

The long-range goal of this project is to elucidate molecular and cellular
mechanisms important in breast cancer causation, utilizing the BALB/c mouse
model and chemical carcinogens.  The approach has been to examine the
expression of endogenous viral (MMTV) genes and cellular oncogenes in
different stages of mammary tumorigenesis.  Our data indicate that multiple
pathways are operative in the genesis of BALB/c mammary tumors.  This
renewal application combines in vivo and in vitro approaches in order to
define general types of molecular and cellular changes that occur at
defined stages in breast cancer development.  We speculate that one
possible initiating event in the process (which can be induced by multiple
agents) may be the altered expression of a trans-regulatory gene, coupled
with the activation of one or more cellular oncogenes by chemical
carcinogen.  The MMTV LTR gene product may sometimes be involved in the
early states of tumorigenesis in BALB/c mice.

The following specific aims are presented.  The first is an extension of in
vivo studies just completed.  The other two aims are new directions that
will be long-term efforts.  1) Multiple transformation assays.  Normal and
preneoplastic mammary cells will be exposed to selected oncogenes that
represent different sites of oncogene action in growth-control pathways
(fos, erb-B, H-ras,neu).  Combinations of oncogenes will be tested to
identify functional activities necessary to mediate complete transformation
of mammary epithelial cells.  A powerful feature of the mouse system is
that the cell phenotypes (normal, preneoplastic, malignant) can be assessed
by transplantation back into cleared mammary fat pads of syngeneic mice,
providing in vivo correlates of in vitro assays.  These studies will also
better define the nature of preneoplastic mammary cells.  2) The structure
and function of the MMTV LTR gene product will be determined.  Protein will
be synthesized using a baculovirus expression vector system and specific
antisera prepared.  Assays using the CAT reporter gene will test if the LTR
protein has trans-acting ability.  Transgenic mice will be made to allow
detailed characterization of the LTR protein.  3) Both in vivo (transgenic
mice) and in vitro  gene or growth-modulating genes display increased
susceptibility to transformation by the chemical carcinogen DMBA.  This
program will provide new understanding of molecular and cellular changes
leading to breast cancer.

## Key facts

- **NIH application ID:** 3171277
- **Project number:** 5R01CA033369-08
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **SAM.gov UEI:** FXKMA43NTV21
- **Principal Investigator:** JANET S BUTEL
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $200,349
- **Award type:** 5
- **Project period:** 1982-09-01 → 1994-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3171277

## Citation

> US National Institutes of Health, RePORTER application 3171277, CARCINOGEN-VIRAL ONCOGENE INTERACTIONS IN MAMMARY CANCER (5R01CA033369-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3171277. Licensed CC0.

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