Published October 12, 2015 | Version v1
Journal article

Frequent down-regulation of ABC transporter genes in prostate cancer

  • 1. Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101 (Lithuania)
  • 2. Urology Centre, Vilnius University, Santariskiu 2, Vilnius, LT-08661 (Lithuania)
  • 3. Faculty of Medicine, Vilnius University, Ciurlionio 21, Vilnius, LT-03101 (Lithuania)

Description

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). 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. 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). The study suggests frequent down-regulation of the ABC transporter genes in PCa, especially in the TMPRSS2-ERG-negative tumors. The online version of this article (doi:10.1186/s12885-015-1689-8) contains supplementary material, which is available to authorized users

Availability note (English)

Available from http://dx.doi.org/10.1186/s12885-015-1689-8; Available from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4603841

Additional details

Publishing Information

Journal Title
BMC cancer (Online)
Journal Volume
15
Journal Page Range
vp.
ISSN
1471-2407

INIS

Country of Publication
United Kingdom
Country of Input or Organization
International Atomic Energy Agency (IAEA)
INIS RN
47084254
Subject category
S62: RADIOLOGY AND NUCLEAR MEDICINE;
Descriptors DEI
GENES; NEOPLASMS; POLYMERASE CHAIN REACTION; PROSTATE
Descriptors DEC
BODY; DISEASES; GENE AMPLIFICATION; GLANDS; MALE GENITALS; ORGANS

Optional Information

Copyright
Copyright (c) Demidenko et al. 2015
Notes
PMCID: PMC4603841; PMID: 26459268; PUBLISHER-ID: 1689; OAI: oai:pubmedcentral.nih.gov:4603841