Accession Number:

ADA413281

Title:

Proto-Oncogene PML and Tumor Evasion in Prostate Cancer

Descriptive Note:

Final rept. 1 Nov 1999-31 Oct 2002

Corporate Author:

OHIO STATE UNIV RESEARCH FOUNDATION COLUMBUS

Personal Author(s):

Report Date:

2002-11-01

Pagination or Media Count:

79.0

Abstract:

This is the Final report on the grant Proto-oncogene PML and tumor evasion in prostate cancer We proposed to identify the antigen presentation defects in human prostate cancer samples and to use mouse prostate cancer model TRAMP mice to study the immune regulation and immune tolerance in prostate cancer. In the past three years, we have completed the experiments proposed in the grant. We have shown that proto-oncogene PML and the major histocompatibility antigen HLA class I are concordantly downregulated in high grade prostate cancer. Using mouse prostate cancer model, we have shown that thymic clonal deletion is a major mechanism for immune tolerance to tumor antigens that previously regarded as prostate specific. We provided the direct evidence that the T cell repertoire specific for tumor antigens can be shaped by negative selection in the thymus. We identified a new novel mechanism for antigen presentation gene regulation, i.e. the degradation of mRNA of an antigen presentation gene was involved in tumor evasion of immune recognition. We analyzed the transcription regulation of one of the antigen presentation genes and identified two new promoter regions and the essential role of the interferon response factor-binding element IRFE in that promoter region. Finally, our preliminary data from chimera mice suggested that distinct thymic cell types expressing peripheral tumor antigen have different roles in determining the range and degree of central and peripheral tolerance.

Subject Categories:

  • Genetic Engineering and Molecular Biology
  • Medicine and Medical Research

Distribution Statement:

APPROVED FOR PUBLIC RELEASE