title: Frequent down-regulation of ABC transporter genes in prostate cancer.
abstract: BACKGROUND
  ATP-binding cassette (ABC) transporters are transmembrane proteins responsible for the efflux of a wide variety of substrates, including steroid metabolites, through the cellular membranes. For better characterization of the role of ABC transporters in prostate cancer (PCa) development, the profile of ABC transporter gene expression was analyzed in PCa and noncancerous prostate tissues (NPT).
  
  
  METHODS
  TaqMan Low Density Array (TLDA) human ABC transporter plates were used for the gene expression profiling in 10 PCa and 6 NPT specimens. ABCB1 transcript level was evaluated in a larger set of PCa cases (N = 78) and NPT (N = 15) by real-time PCR, the same PCa cases were assessed for the gene promoter hypermethylation by methylation-specific PCR.
  
  
  RESULTS
  Expression of eight ABC transporter genes (ABCA8, ABCB1, ABCC6, ABCC9, ABCC10, ABCD2, ABCG2, and ABCG4) was significantly down-regulated in PCa as compared to NPT, and only two genes (ABCC4 and ABCG1) were up-regulated. Down-regulation of ABC transporter genes was prevalent in the TMPRSS2-ERG-negative cases. A detailed analysis of ABCB1 expression confirmed TLDA results: a reduced level of the transcript was identified in PCa in comparison to NPT (p = 0.048). Moreover, the TMPRSS2-ERG-negative PCa cases showed significantly lower expression of ABCB1 in comparison to NPT (p = 0.003) or the fusion-positive tumors (p = 0.002). Promoter methylation of ABCB1 predominantly occurred in PCa and was rarely detected in NPT (p < 0.001).
  
  
  CONCLUSIONS
  The study suggests frequent down-regulation of the ABC transporter genes in PCa, especially in the TMPRSS2-ERG-negative tumors.
authors.affiliation: Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. rita.demidenko@gmail.com.
authors.forename: Rita
authors.initials: R
authors.lastname: Demidenko
authors.affiliation: Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. dei.razanauskas@gmail.com.
authors.forename: Deividas
authors.initials: D
authors.lastname: Razanauskas
authors.affiliation: Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. kristina.daniunaite@gf.vu.lt.
authors.forename: Kristina
authors.initials: K
authors.lastname: Daniunaite
authors.affiliation: Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. juozas.lazutka@gf.vu.lt.
authors.forename: Juozas Rimantas
authors.initials: JR
authors.lastname: Lazutka
authors.affiliation: Faculty of Medicine, Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. feliksas.jankevicius@santa.lt.|Urology Centre, Vilnius University, Santariskiu 2, Vilnius, LT-08661, Lithuania. feliksas.jankevicius@santa.lt.
authors.forename: Feliksas
authors.initials: F
authors.lastname: Jankevicius
authors.affiliation: Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. sonata.jarmalaite@gf.vu.lt.
authors.forename: Sonata
authors.initials: S
authors.lastname: Jarmalaite
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D016000:Cluster Analysis; D018899:CpG Islands; D019175:DNA Methylation; D015536:Down-Regulation; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D005810:Multigene Family; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D024363:Transcription Initiation Site
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D018528:ATP-Binding Cassette Transporters