# ANTIESTROGEN/5-FU DRUG COMBINATIONS IN BREAST CANCER

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 1990 · $139,611

## Abstract

Basic research remains critical for our interpretation and improvement of
ongoing chemo-endocrine breast cancer protocols.  Our prototype model of
tamoxifen-5fluorouracil (TAM-FUra) modulation remains the only in vitro
example of chemo-endocrine synergy reported to date, and this project will
continue to explore oncogenes (c-myc, c-fos, c-erbB-2) and estrogen
receptors (ER) as targets for RNA-directed chemo-endocrine therapy.  Human
breast cancer cell lines will be used to i) complete studies comparing
antiestrogen effects on c-myc and c-fos expression, ii) establish the
therapeutic impact of inhibiting endogenous c-erbB-2 expression by
transfecting antisense-erbB-2 genes, and iii) identify and characterize the
small RNA species (RNAt) isolated from in vitro bound complexes of ER with
its cognate DNA response element, ERE.  Northern blot hybridization,
nuclear run-on and in vitro transcript splicing assays will differentiate
effects on c-myc and c-fos mRNA metabolism resulting from anti-estrogen
therapy; and modulation of protein kinase C activity will help to determine
if this signal transduction pathway is involved in these antiestrogen
effects.  Transfection of a constitutively promoted 5'-antisense-erbB-2
vector appears to inhibit growth of only those breast cancer cells showing
deregulated endogenous c-erbB-2 overexpression; and further analysis of
sense vs. antisense transfected subclones is necessary to document changes
induced in c-erbB-2 transcript rates, mRNA and protein (pl85erbB-2) levels.
Antisense-erbB-2 genes driven by inducible promoters (MMTV, hsp-70) will
also be constructed to deliver the antisense response in combination with
drug or endocrine therapy.  Lastly, preliminary studies support a new model
of ER gene activation involving a 4S RNA species (RNAt) that is necessary
for and contained within in vitro ER-ERE complexes.  Gel-shift will be used
to purify RNAt, and to characterize its binding with ER and ERE.  A
therapeutic role for RNAt will be looked for by comparing drug and
endocrine effects on ER-ERE complexes formed either in vitro or in vivo.
These studies will hopefully provide new rationale and direction for
improved chemo-endocrine therapies of breast cancer.

## Key facts

- **NIH application ID:** 3174333
- **Project number:** 2R01CA036773-07
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **SAM.gov UEI:** KMH5K9V7S518
- **Principal Investigator:** Christopher Benz
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1990
- **Award amount:** $139,611
- **Award type:** 2
- **Project period:** 1983-08-15 → 1995-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3174333

## Citation

> US National Institutes of Health, RePORTER application 3174333, ANTIESTROGEN/5-FU DRUG COMBINATIONS IN BREAST CANCER (2R01CA036773-07). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3174333. Licensed CC0.

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