Genetic Risk Factor for Prostate Cancer

Abstract

NKX3.1 is a homeoprotein with prostate-specific expression in adults. Loss of NKX3.1 correlates with prostate cancer progression. NKX3.1 protein expression is reduced to varying degrees in virtually all primary prostate cancers. The NKX3.1 gene is affected by deletion and/or promoter hypermethylation in 90% of primary prostate cancers. NKX3.1 acts as a transcription factor by binding directly to DNA. NKX3.1 also complexes and coactivates other transcription factors such as serum response factor. We have now found that NKX3.1 complexes with the DNA unwinding enzyme topoisomerase I. NKX3.1 binds to topoisomerase I in a stoichiometric relationship and enhances scissile strand DNA cleavage by topoisomerase I. NKX3.1 does not affect religation of relaxed DNA by topoisomerase I. We also found that NKX3.1 mediates DNA damage repair after cells are exposed to gamma-irradiation. The effect on DNA repair is mediated in cooperation with topoisomerase I. Loss of NKX3.1 expression that occurs early in prostate cancer may predispose to DNA damage and thereby facilitate prostate cancer progression.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2005
Accession Number
ADA434784

Entities

People

  • Edward P. Gelmann

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Alkaloids
  • Amino Acids
  • Biomedical Research
  • Carrier Proteins
  • Cell Line
  • Cells
  • Chemistry
  • Dissociation
  • Gel Electrophoresis
  • Liquid Chromatography
  • Neoplasms
  • Peptides
  • Prostate Cancer
  • Protein-Protein Interactions
  • Proteins
  • Risk Factors
  • Transcription Factors

Fields of Study

  • Biology

Readers

  • Molecular Biology and Genetics
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology