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BMC Cancer. 2015 Oct 12;15:683. doi: 10.1186/s12885-015-1689-8.

Frequent down-regulation of ABC transporter genes in prostate cancer.

Author information

1
Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. rita.demidenko@gmail.com.
2
Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. dei.razanauskas@gmail.com.
3
Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. kristina.daniunaite@gf.vu.lt.
4
Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. juozas.lazutka@gf.vu.lt.
5
Faculty of Medicine, Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. feliksas.jankevicius@santa.lt.
6
Urology Centre, Vilnius University, Santariskiu 2, Vilnius, LT-08661, Lithuania. feliksas.jankevicius@santa.lt.
7
Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. sonata.jarmalaite@gf.vu.lt.

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.

PMID:
26459268
PMCID:
PMC4603841
DOI:
10.1186/s12885-015-1689-8
[Indexed for MEDLINE]
Free PMC Article

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