Abstract
BackgroundATP-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).MethodsTaqMan 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.ResultsExpression 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).ConclusionsThe study suggests frequent down-regulation of the ABC transporter genes in PCa, especially in the TMPRSS2-ERG-negative tumors.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-015-1689-8) contains supplementary material, which is available to authorized users.
Highlights
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
ABCB1 expression has been related to the efflux of androgens from prostate cancer (PCa) cell lines [10] suggesting that reduced levels of ABCB1 might be responsible for intratumoral androgen accumulation and sustained signaling from androgen receptors (ARs) [4]
Gene expression profile of ABC transporters in PCa In order to explore the expression levels of the ABC genes, 10 PCa and 6 noncancerous prostate tissues (NPT) samples were profiled on human ABC transporter TaqMan Low Density Array (TLDA) containing probes for 50 ABC genes in total
Summary
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. ATP-binding cassette (ABC) transporters are transmembrane proteins responsible for the transfer of a wide variety of substrates through the extra- and intra-cellular membranes [1]. ABCA1, another important transporter of the ABC family, was recently shown to be related to the development of aggressive PCa through the impaired efflux of cholesterol, an alternative source for androgen synthesis [11]. Expression of several ABC transporters was shown to be regulated by androgens or ARs [15, 16]
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