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Sökning: WFRF:(Cunliffe V. T.) > (2019) > Increased EZH2 expr...

  • Wu, X. N.University of Oxford (författare)

Increased EZH2 expression in prostate cancer is associated with metastatic recurrence following external beam radiotherapy

  • Artikel/kapitelEngelska2019

Förlag, utgivningsår, omfång ...

  • 2019-05-18
  • Wiley,2019

Nummerbeteckningar

  • LIBRIS-ID:oai:gup.ub.gu.se/281881
  • https://gup.ub.gu.se/publication/281881URI
  • https://doi.org/10.1002/pros.23817DOI
  • https://lup.lub.lu.se/record/7603714f-e0f4-40de-83b9-c48ea5a8fa9aURI

Kompletterande språkuppgifter

  • Språk:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • Background Enhancer of zeste 2 (EZH2) promotes prostate cancer progression. We hypothesized that increased EZH2 expression is associated with postradiotherapy metastatic disease recurrence, and may promote radioresistance. Methods EZH2 expression was investigated using immunohistochemistry in diagnostic prostate biopsies of 113 prostate cancer patients treated with radiotherapy with curative intent. Associations between EZH2 expression in malignant and benign tissue in prostate biopsy cores and outcomes were investigated using univariate and multivariate Cox regression analyses. LNCaP and PC3 cell radiosensitivity was investigated using colony formation and gamma H2AX assays following UNC1999 chemical probe-mediated EZH2 inhibition. Results While there was no significant association between EZH2 expression and biochemical recurrence following radiotherapy, univariate analysis revealed that prostate cancer cytoplasmic and total EZH2 expression were significantly associated with metastasis development postradiotherapy (P = 0.034 and P = 0.003, respectively). On multivariate analysis, the prostate cancer total EZH2 expression score remained statistically significant (P = 0.003), while cytoplasmic EZH2 expression did not reach statistical significance (P = 0.053). No association was observed between normal adjacent prostate EZH2 expression and biochemical recurrence or metastasis. LNCaP and PC3 cell treatment with UNC1999 reduced histone H3 lysine 27 tri-methylation levels. Irradiation of LNCaP or PC3 cells with a single 2 Gy fraction with UNC1999-mediated EZH2 inhibition resulted in a statistically significant, though modest, reduction in cell colony number for both cell lines. Increased gamma H2AX foci were observed 24 hours after ionizing irradiation in LNCaP cells, but not in PC3, following UNC1999-mediated EZH2 inhibition vs controls. Conclusions Taken together, these results reveal that high pretreatment EZH2 expression in prostate cancer in diagnostic biopsies is associated with an increased risk of postradiotherapy metastatic disease recurrence, but EZH2 function may only at most play a modest role in promoting prostate cancer cell radioresistance.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Scott, H.University of Oxford (författare)
  • Carlsson, Sigrid,1982Gothenburg University,Göteborgs universitet,Institutionen för kliniska vetenskaper, Avdelningen för urologi,Institute of Clinical Sciences, Department of Urology,Sahlgrenska Academy,Memorial Sloan-Kettering Cancer Center(Swepub:lu)si5270ca (författare)
  • Sjoberg, D. D.Memorial Sloan-Kettering Cancer Center (författare)
  • Cerundolo, L.University of Oxford (författare)
  • Lilja, HansLund University,Lunds universitet,Klinisk kemi, Malmö,Forskargrupper vid Lunds universitet,Clinical Chemistry, Malmö,Lund University Research Groups,Memorial Sloan-Kettering Cancer Center(Swepub:lu)klke-hli (författare)
  • Prevo, R.University of Oxford (författare)
  • Rieunier, G.University of Oxford (författare)
  • Macaulay, V.University of Oxford (författare)
  • Higgins, G. S. (författare)
  • Verrill, C. L.University of Oxford (författare)
  • Lamb, A. D.University of Oxford (författare)
  • Cunliffe, V. T.University of Sheffield (författare)
  • Bountra, C.University of Oxford (författare)
  • Hamdy, F. C.University of Oxford (författare)
  • Bryant, R. J.University of Oxford (författare)
  • University of OxfordInstitutionen för kliniska vetenskaper, Avdelningen för urologi (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:Prostate: Wiley79:10, s. 1079-10890270-4137
  • Ingår i:The Prostate: Wiley79:10, s. 1079-10891097-0045

Internetlänk

Hitta via bibliotek

  • Prostate (Sök värdpublikationen i LIBRIS)

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