title: The analysis of serum response factor expression in bone and soft tissue prostate cancer metastases.
abstract: BACKGROUND
  Castration-resistant prostate cancer (CRPC) represents a challenge to treat with no effective treatment options available. We recently identified serum response factor (SRF) as a key transcription factor in an in vitro model of castration resistance where we showed that SRF inhibition resulted in reduced cellular proliferation. We also demonstrated an association between SRF protein expression and CRPC in a cohort of castrate-resistant transurethral resections of the prostate (TURPS). The mechanisms regulating the growth of CRPC bone and visceral metastases have not been explored in depth due to the paucity of patient-related material available for analysis. In this study, we aim to evaluate SRF protein expression in prostate cancer (PCa) metastases, which has not previously been reported.
  
  
  RESULTS
  We evaluated the nuclear tissue expression profile of SRF by immunohistochemistry in 151 metastatic sites from 42 patients who died of advanced PCa. No relationship between SRF nuclear expression and the site of metastasis was observed (P = 0.824). However, a negative association between SRF nuclear expression in bone metastases and survival from (a) diagnosis with PCa (P = 0.005) and (b) diagnosis with CRPC (P = 0.029) was seen. These results demonstrate that SRF nuclear expression in bone metastases is associated with survival, with patients with the shortest survival showing high SRF nuclear expression and patients with the longest survival having low SRF nuclear expression.
  
  
  CONCLUSIONS
  Our study indicates that SRF is a key factor determining patients' survival in metastatic CRPC and therefore may represent a promising target for future therapies.
authors.affiliation: OncoMark Ltd, Nova UCD, University College Dublin, Belfield, Dublin 4, Ireland; Department of Pathology, RCSI Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
authors.forename: Gillian
authors.initials: G
authors.lastname: O'Hurley
authors.forename: Maria
authors.initials: M
authors.lastname: Prencipe
authors.forename: Dara
authors.initials: D
authors.lastname: Lundon
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Neill
authors.forename: Susie
authors.initials: S
authors.lastname: Boyce
authors.forename: Anthony
authors.initials: A
authors.lastname: O'Grady
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.forename: Colm
authors.initials: C
authors.lastname: Morrissey
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.forename: R William G
authors.initials: RW
authors.lastname: Watson
mesh_terms: D001859:Bone Neoplasms / Q000737:chemistry* / Q000556:secondary*; D002467:Cell Nucleus / Q000737:chemistry; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D011467:Prostate / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000737:chemistry* / Q000401:mortality; D064129:Prostatic Neoplasms, Castration-Resistant / Q000737:chemistry* / Q000401:mortality / Q000473:pathology; D026362:Serum Response Factor / Q000032:analysis*; D015996:Survival Rate
chemical_list: D026362:Serum Response Factor
keywords: immunohistochemistry; prostate cancer metastases; serum response factor