MMTV GENE PRODUCTS AND TRANSFORMATION

Project: Research project

Project Details

Description

We will investigate the role of the protein producs of the long terminal
repeat (LTR) region of mouse mammary tumor virus (MMTV) in the life cycle
of MMTV, and in tumorigenesis by MMTV. The transformation-specific
characteristics of spontaneous T cells leukemias of DBA/2 mice (ML cells)
will be studied, and the possible leukemogenic activity of MMTV
investigated. We will raise antisera against synthetic peptides predicted
by the LTR open reading frame, and an expression vector containing MMTV LTR
sequences will be used to obtain purified LTR protein for polyclonal
antiserum, and monoclonal antibody production. These reagents will be used
to analyze normal and neoplastic mouse tissues for the expression and
distribution of pLTRs. The effect of various hormones on the expression of
pLTR will be tested in primary cultures of mouse tissues growing on
floating collagen gels.

The role of MMTV in ML cells will be investigated by analyzing MMTV LTR
specific mRNAs that are transcribed in high levels in these cells. We will
test whether acquired deleted proviruses with truncated LTRs are a
consistent feature of ML cells. Acquired deleted proviruses will be cloned
in order to define the deletions in the LTR. The leukemogenic potential of
MMTV will be tested by intrathymic injection of young DBA/2 mice with the
milk virus. ML cells will also be examined for the presence of MCF like
proviruses, and enhanced expression of known oncogenes.

The 15,000 Mr transformation-specific protein of ML cells, that is detected
by using the NIH-3T3 transfection assay, will be characterized, and DNA
sequences encoding it will be cloned. The cloned gene will be used to probe
for enhanced expression in tumor tissues, association with proviruses and
homology to any of the known oncogenes.

Since the LTR region of MMTV probably plays an essential role in the
transforming activity of MMTV, it is essential for the understanding of
tumorigenesis by MMTV, that the role of the LTR gene product be
understood. The study of ML cells might contribute to an understanding of
the mechanism of transformation by slowly transforming retroviruses, and
should add to our understanding of oncogenesis.
StatusFinished
Effective start/end date4/1/853/31/86

Funding

  • National Cancer Institute

ASJC

  • Molecular Biology
  • Cancer Research
  • Biotechnology
  • Histology
  • Immunology

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