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13:19
Microarray-based Identification of Individual HERV Loci Expression: Application to Biomarker Discovery in Prostate Cancer
Published on: November 2, 2013
Selective changes of retroelement expression in human prostate cancer
Wolfgang Goering1, Teodora Ribarska, Wolfgang A Schulz
1Department of Urology, Heinrich Heine University, Düsseldorf, Germany.
Carcinogenesis
|August 11, 2011
Summary
Retroelements are reactivated in prostate cancer, with specific human endogenous retrovirus-K (HERV-K) proviruses showing increased expression and decreased DNA methylation. This suggests a role for HERV-K in prostate carcinogenesis.
Area of Science:
- Genomics
- Epigenetics
- Cancer Biology
Background:
- Retroelements comprise a significant portion of the human genome and are typically silenced in healthy cells.
- Genome-wide DNA hypomethylation in cancer may lead to retroelement re-expression, but this is poorly understood in human cancers.
Purpose of the Study:
- To investigate the expression and DNA methylation patterns of various retroelements in human prostate cancer.
- To determine if retroelement re-expression occurs in prostate cancer and its correlation with DNA methylation status.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to measure retroelement expression.
- Pyrosequencing was employed to assess DNA methylation levels in retroelement regions, particularly long terminal repeats (LTRs).
Main Results:
- A striking, generalized increase in HERV-K_22q11.23 provirus expression was observed in prostate cancers, including novel spliced Np9 transcript expression in some tumors, alongside decreased LTR DNA methylation.
- Conversely, HERVK17 expression was significantly reduced in cancer tissues, independent of LTR methylation changes.
- LINE-1 expression decreased in prostate cancers despite promoter hypomethylation, while young Alu elements (AluYa5, AluYb8) showed increased expression in individual tumors.
Conclusions:
- Prostate cancer exhibits specific alterations in retroelement expression and DNA methylation, challenging the notion of generalized retroelement overexpression due to hypomethylation.
- Specific human endogenous retrovirus-K (HERV-K) proviruses demonstrate significant expression changes in prostate cancer, suggesting potential functional roles in carcinogenesis.
- Androgen receptor binding to steroid hormone-responsive elements in LTRs of androgen-responsive prostate cancer cell lines indicates a potential link between hormonal regulation and retroelement activity.
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