{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T19:18:55Z","timestamp":1791314335029,"version":"4.3.1"},"reference-count":39,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2008,9,16]],"date-time":"2008-09-16T00:00:00Z","timestamp":1221523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Intl Journal of Cancer"],"published-print":{"date-parts":[[2008,12,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Gene fusions between prostate\u2010specific, androgen responsive <jats:italic>TMPRSS2<\/jats:italic> gene and oncogenic ETS factors, such as <jats:italic>ERG<\/jats:italic>, occur in up to 50% of all prostate cancers. We recently defined a gene signature that was characteristic to prostate cancers with <jats:italic>ERG<\/jats:italic> activation. This suggested epigenetic reprogramming, such as upregulation of histone deactylase 1 (<jats:italic>HDAC1<\/jats:italic>) gene and downregulation of its target genes. We then hypothesized that patients with <jats:italic>ERG<\/jats:italic>\u2010positive prostate cancers may benefit from epigenetic therapy such as HDAC inhibition (HDACi), especially in combination with antiandrogens. Here, we exposed <jats:italic>ERG<\/jats:italic>\u2010positive prostate cancer cell lines to HDAC inhibitors Trichostatin A (TSA), MS\u2010275 and suberoylanilide hydroxamic acid (SAHA) with or without androgen deprivation. We explored the effects on cell phenotype, gene expression as well as ERG and androgen receptor (AR) signaling. When compared with 5 other prostate cell lines, <jats:italic>ERG<\/jats:italic>\u2010positive VCaP and DuCap cells were extremely sensitive to HDACi, in particular TSA, showing synergy with concomitant androgen deprivation increasing apoptosis. Both of the HDAC inhibitors studied caused repression of the <jats:italic>ERG<\/jats:italic>\u2010fusion gene, whereas the pan\u2010HDAC inhibitor TSA prominently repressed the <jats:italic>ERG<\/jats:italic>\u2010associated gene signature. Additionally, HDACi and flutamide caused retention of AR in the cytoplasm, indicating blockage of androgen signaling. Our results support the hypothesis that HDACi, especially in combination with androgen deprivation, is effective against <jats:italic>TMPRSS2\u2010ERG<\/jats:italic>\u2010fusion positive prostate cancer <jats:italic>in vitro<\/jats:italic>. Together with our previous <jats:italic>in vivo<\/jats:italic> observations of an \u201cepigenetic reprogramming gene signature\u201d in clinical <jats:italic>ERG<\/jats:italic>\u2010positive prostate cancers, these studies provide mechanistic insights to <jats:italic>ERG<\/jats:italic>\u2010associated tumorigenesis and suggest therapeutic paradigms to be tested <jats:italic>in vivo<\/jats:italic>. \u00a9 2008 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ijc.23885","type":"journal-article","created":{"date-parts":[[2008,9,16]],"date-time":"2008-09-16T20:04:34Z","timestamp":1221595474000},"page":"2774-2781","source":"Crossref","is-referenced-by-count":54,"title":["Defining the molecular action of HDAC inhibitors and synergism with androgen deprivation in ERG\u2010positive prostate cancer"],"prefix":"10.1002","volume":"123","author":[{"given":"Mari","family":"Bj\u00f6rkman","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristiina","family":"Iljin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasi","family":"Halonen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henri","family":"Sara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Kaivanto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Nees","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olli 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