Frequent down-regulation of ABC transporter genes in prostate cancer

Rita Demidenko1, Deividas Razanauskas2, Kristina Daniunaite3

  • 1Division of Human Genome Research Centre, Faculty of Nature Sci., Vilnius University, Ciurlionio 21, Vilnius, LT-03101, Lithuania. rita.demidenko@gmail.com.

BMC Cancer
|October 14, 2015
PubMed
Abstract

Insights

ATP-binding cassette (ABC) transporters are frequently down-regulated in prostate cancer (PCa), particularly in TMPRSS2-ERG-negative tumors. This suggests a potential role for ABC transporter gene expression in PCa development and progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • ATP-binding cassette (ABC) transporters are crucial transmembrane proteins involved in substrate efflux.
  • Their role in prostate cancer (PCa) development necessitates a detailed analysis of their gene expression profiles.

Purpose of the Study:

  • To investigate the gene expression profile of ABC transporters in prostate cancer (PCa) and non-cancerous prostate tissues (NPT).
  • To identify specific ABC transporter genes altered in PCa and their correlation with tumor characteristics, such as TMPRSS2-ERG fusion status.

Main Methods:

  • Gene expression profiling of ABC transporters was performed using TaqMan Low Density Array (TLDA) on PCa and NPT specimens.
  • Real-time PCR was employed to validate ABCB1 transcript levels in a larger cohort.
  • Methylation-specific PCR assessed ABCB1 promoter hypermethylation in PCa and NPT.

Main Results:

  • Eight ABC transporter genes (ABCA8, ABCB1, ABCC6, ABCC9, ABCC10, ABCD2, ABCG2, ABCG4) were significantly down-regulated in PCa compared to NPT.
  • ABCB1 transcript levels were reduced in PCa, with significantly lower expression in TMPRSS2-ERG-negative cases.
  • Promoter hypermethylation of ABCB1 was predominantly observed in PCa tissues.

Conclusions:

  • Prostate cancer is characterized by frequent down-regulation of ABC transporter genes.
  • The down-regulation is particularly pronounced in TMPRSS2-ERG-negative PCa, suggesting a specific mechanism involving these tumors.
  • ABCB1 gene expression and its promoter methylation status are significantly altered in PCa.

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