Identification of Prostate Cancer-Related Genes Using Inhibition of NMD in Prostate Cancer Cell Lines

Abstract

A strategy to identify mutant genes using inhibition of nonsense mediated decay (NMD) in cell lines has been proposed by others. Blocking translation with antibiotic emetine has been shown to inhibit the NMD. Stabilization of mutant mRNA following the inhibition of NMD with emetine can be detected using microarray technology, such as Affymetrix genechips, for example. Unfortunately, too many genes that do not contain any mutations show mRNA increase following emetine treatment due to stress response to the inhibition of translation or due to being a natural substrate for NMD, thus complicating the identification of mutant genes. We have developed a simple analytical method that increases the efficiency of identifying mutant genes in cell lines following inhibition of nonsense mediated decay (NMD). The approach assumes that the spectra of mutant genes differ between cell lines of the same tumor origin. Using this analytical filter we have identified previously unknown inactivating mutations in the Jak1, Synaptojanin2 (SYNJ2) and Cleft Lip and Palate Transmembrane Protein 1(CLPTM1) genes in the prostate cancer cell line LANCaP. A list of candidate genes for sequencing analysis has been generated for the other prostate cancer cell lines.

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Document Details

Document Type
Technical Report
Publication Date
Jan 01, 2005
Accession Number
ADA435274

Entities

People

  • Yurij Ionov

Organizations

  • Health Research, Incorporated

Tags

DTIC Thesaurus Topics

  • Biomedical Research
  • Cancer
  • Colon
  • Colon Cancer
  • Dna Microarrays
  • Epithelial Cells
  • Gene Expression
  • Genetic Code
  • Genetics
  • Genomic Instability
  • Inhibition
  • Microarray Analysis
  • Prostate Cancer
  • Proteins
  • Rna Stability
  • Sequence Analysis
  • Transcription Factors

Fields of Study

  • Biology

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular Genetics
  • Molecular and genetic basis of cancer.