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.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jan 01, 2004
- Accession Number
- ADA422932
Entities
People
- Edward P. Gelmann
Organizations
- Georgetown University