# GENETIC AND MOLECULAR ANALYSIS OF STEROID RESPONSIVENESS

> **NIH NIH R01** · TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR · 1991 · $137,391

## Abstract

Specific aspects of glucocorticoid-regulated transcription of the proviral
genes of mouse mammary tumor virus (MMTV) will be investigated to address
the long range goals of understanding the molecular mechanisms by which
steroid hormones affect gene expression.  A combination of molecular and
genetic approaches will be taken with continuous tissue culture cell
lines.  Preliminary evidence has indicated that the MMTV long terminal
repeat (LTR) contains a negative regulatory element that decreases
transcription from the MMTV promoter in the absence of glucocorticoids; the
function of this element may be to maintain regulated genes in an inactive
state in the absence of hormone.  The DNA sequences required for this
negative element will be defined, and the element will be characterized
with regard to its position, orientation and promoter specificity and its
requirement for specific trans-acting factors utilizing transient
expression assays.  A number of endogenous MMTV proviral genes have been
isolated by molecular cloning; these endogenous genes are normally not
transcriptionally active.  The ability of the LTRs of these isolated genes
to function as regulated promoters will be compared in a defined
experimental context to assess the relative extent to which DNA sequence
defects and chromosomal position effects contribute to the lack of
endogenous gene expression.  The function of the LTRs in vivo will be
correlated with the DNA sequence of regulatory elements and with
glucocorticoid receptor binding in vitro.  The potential role of DNA
methylation in controlling the potential for steroid-regulated
transcription will be investigated.  Variants in glucocorticoid-responsive
gene expression will be selected that take advantage of selectable markers
expressed from the MMTV promoter.  The proposed experiments will explore
the molecular basis of regulatory and developmental phenomena that are
potentially related to many human diseases.  In addition, the increased
understanding of transcriptional regulatory elements within the MMTV LTRs
may aid in elucidating the mechanism of viral tumorigenesis.

## Key facts

- **NIH application ID:** 3170570
- **Project number:** 5R01CA032695-08
- **Recipient organization:** TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
- **SAM.gov UEI:** HFT7XTHB6563
- **Principal Investigator:** DAVID O PETERSON
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1991
- **Award amount:** $137,391
- **Award type:** 5
- **Project period:** 1982-07-01 → 1995-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3170570

## Citation

> US National Institutes of Health, RePORTER application 3170570, GENETIC AND MOLECULAR ANALYSIS OF STEROID RESPONSIVENESS (5R01CA032695-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3170570. Licensed CC0.

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