LEUKEMOGENESIS BY MURINE RETROVIRUSES

Project: Research project

Project Details

Description

Replication-competent murine retroviruses induce various types of
hematopoietic tumors upon inoculation into mice. Recombination studies
using molecularly cloned, viral genomes show that the long terminal repeat
(LTR) is the primary genetic determinant of the viral disease inducing
phenotype. Transcriptional tissue specificity of several viral LTRs shows
an excellent correlation with the type of tumor induced by each virus. The
central focus of the work described in this proposal is an assessment of the
role of tissue specific differences in transcriptional activity in
leukemogenicity. The nature of the molecular events involved in tissue
specificity will be studied in detail primarily using the thymomagenic
virus, SL3-3, and the non-leukemogenic virus, Akv. These studies will focus
on identification of sequences at the single nucleotide level that are
responsible for differences in tissue specificity and on identification of
proteins that interact differentially with enhancer elements in the LTR.
These studies are expected to lead to insight into the normal regulation of
cell-type specific gene expression. The means which tissue specific
regulation of gene expression alters viral leukemogenicity will also be
studied in detail. From the standpoint of viral genetics, these studies are
aimed at identifying the minimal changes necessary to convert a non-
leukemogenic virus into one that induces thymic lymphomas. Two mechanisms
by which altered tissue specificity could determine leukemogenicity will be
investigated. One is whether transcriptional elements alter viral tissue
tropism, while the other is whether these elements alter oncogene expression
in a manner that alters tumorigenicity.
StatusFinished
Effective start/end date12/31/8911/30/06

Funding

  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute
  • National Cancer Institute: $362,843.00
  • National Cancer Institute
  • National Cancer Institute: $371,575.00
  • National Cancer Institute: $297,372.00
  • National Cancer Institute
  • National Cancer Institute: $372,132.00

ASJC

  • Medicine(all)
  • Cancer Research
  • Virology
  • Genetics
  • Molecular Biology

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