# REGULATION OF MMTV IN T-CELL TUMORS

> **NIH NIH R01** · UNIVERSITY OF TEXAS AT AUSTIN · 1992 · $186,937

## Abstract

The mouse mammary tumor virus (MMTV) is a B type retrovirus which causes
primarily mammary carcinomas in mice.  The MMTV long terminal repeat (LTR)
has an unusual 1200 bp U3 region containing the transcription regulatory
signals of the virus as well as a long open reading frame (orf) potentially
encoding a protein of 36 kD.  This orf is conserved in all known MMTV
strains and the observed base substitutions give largely conservative or
silent amino acid changes; this suggests conservation of protein function.
In addition, a 1.7 kb spliced transcript which has the appropriate
structure for orf mRNA has been identified in mammary glands and tumors
from high mammary cancer mouse strains.  Although orf has been reported to
be a viral transactivator, this has not been confirmed, and the orf product
has not been identified.  Very recently we have overexpressed the unfused
MMTV orf product from a recombinant baculovirus in insect cells.  Because
the 36 kD orf product appears to be a nuclear protein, we have speculated
that orf is a positive or negative regulator of transcription which
participates indirectly or cooperatively in MMTV-induced tumors.  Several
approaches will be used to test this hypothesis.  In a genetic approach, we
will construct an MMTV provirus which is incapable of orf synthesis for
analysis of its replication potential in culture.  Transgenic mice
overexpressing the orf product will be assessed for the tissue-specific
expression of orf, level of endogenous MMTV RNA, and the incidence of
spontaneous tumors.  In another approach, we will use the baculovirus-
produced orf protein to develop polyclonal antibodies needed for
identification and characterization of the orf product in mammalian cells
expressing integrated MMTV proviruses.  The baculovirus-produced protein
also will be used for biochemical analysis.  The intracellular location and
posttranslational modifications of orf will be examined in insect cells,
and partially purified orf will be used to evaluate the nucleic acid
binding properties of the protein.  Finally, the baculovirus orf protein
will be employed in in vitro transcription reactions to determine if orf
has either positive or negative effects on MMTV transcription.  Because of
the unusual nature of the MMTV orf and the general conservation of viral
genetic information, it is likely that orf plays a unique role in MMTV
replication or tumorigenesis.

## Key facts

- **NIH application ID:** 3172591
- **Project number:** 5R01CA034780-08
- **Recipient organization:** UNIVERSITY OF TEXAS AT AUSTIN
- **SAM.gov UEI:** V6AFQPN18437
- **Principal Investigator:** Jaquelin Page Dudley
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1992
- **Award amount:** $186,937
- **Award type:** 5
- **Project period:** 1984-07-01 → 1994-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3172591

## Citation

> US National Institutes of Health, RePORTER application 3172591, REGULATION OF MMTV IN T-CELL TUMORS (5R01CA034780-08). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3172591. Licensed CC0.

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