Dept. of Urology, Medical Faculty, Heinrich Heine University, Düsseldorf, Germany.
Retroelements constitute a large part of the human genome. These sequences are mostly silenced in normal cells, but genome-wide DNA hypomethylation in cancers might lead to their reexpression. Whether this reexpression really occurs in human cancers is largely unkown. We therefore investigated expression and DNA methylation of several classes of retroelements in human prostate cancer tissues and cell lines by quantitative RT-PCR and pyrosequencing, respectively. The most striking finding was strong and generalized increased expression of the HERV-K_22q11.23 provirus in cancers, including de novo-expression of a spliced accessory Np9 transcript in some tumors. In parallel, DNA methylation in the LTR decreased. Conversely, HERVK17 expression was significantly diminished in cancer tissues, but this decrease was unrelated to LTR methylation. Expression of both proviruses was restricted to androgen-responsive prostate cancer cell lines and LTRs sequences containing steroid hormone responsive elements bound the androgen receptor and conferred androgen responsiveness to reporter constructs. Expression of LINE-1 5'-UTR and 3'-UTR sequences in prostate cancers rather decreased, despite significant hypomethylation of the internalLINE-1 promoter. Increased expression of the young AluYa5 and AluYb8 families was restricted to individual tumors. Our findings demonstrate a surprising specificity of changes in expression and DNA methylation of retroelements in prostate cancer. In particular, LINE-1 hypomethylation does not lead to generalized overexpression, but specific HERV-K proviruses display conspicuous changes in their expression hinting at significant functions during prostate carcinogenesis.
Written by:
Goering W, Ribarska T, Schulz WA. Are you the author?
Reference: Carcinogenesis. 2011 Aug 8. Epub ahead of print.
doi: 10.1093/carcin/bgr181
PubMed Abstract
PMID: 21828060
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