Genetics Risk Factor for Prostate Cancer

Abstract

NKX3.l is a homeoprotein with prostate-specific expression in adults. Loss of NKX3.l correlates with prostate cancer progression. NKX3.l protein expression is reduced to varing degrees in virtually all primary prostate cancers. The NKX3.l gene is affected by deletion and/or promoter hypermethylation in 90% of primary prostate cancers. NKX3.l acts as a transcription factor by binding directly to DNA. NKX3.l also complexes and coactivates other transcription factors such as serum response factor. We have now found that NKX3.l complexes with the DNA unwinding enzyme toposiomerase I. NKX3.l binds to toposiomerase I in a stoichiometric relationship and enhances scissile strand DNA cleavage by toposiomerase I. NKX3.l does not affect religation of relaxed DNA by toposiomerase I. Toposiomerase I is involved in DNA replication, transcription, and repair and may be nder significant control of NKX3.1 in prostate epithelial cells.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2004
Accession Number
ADA422932

Entities

People

  • Edward P. Gelmann

Organizations

  • Georgetown University

Tags

DTIC Thesaurus Topics

  • Carrier Proteins
  • Cells
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Genetics
  • Mass Spectrometers
  • Mass Spectrometry
  • Neoplasms
  • Nucleotides
  • Organic Chemistry
  • Prostate Cancer
  • Proteins
  • Risk Factors

Fields of Study

  • Biology

Readers

  • Computer Engineering
  • Molecular and Cellular Biochemistry
  • Molecular and genetic basis of cancer.

Technology Areas

  • Biotechnology