title: Relationship between serum response factor and androgen receptor in prostate cancer.
abstract: BACKGROUND
  Serum response factor (SRF) is an important transcription factor in castrate-resistant prostate cancer (CRPC). Since CRPC is associated with androgen receptor (AR) hypersensitivity, we investigated the relationship between SRF and AR.
  
  
  METHODS
  Transcriptional activity was assessed by luciferase assay. Cell proliferation was measured by MTT and flow cytometry. Protein expression in patients was assessed by immunohistochemistry.
  
  
  RESULTS
  To investigate AR involvement in SRF response to androgen, AR expression was down-regulated using siRNA. This resulted in the abrogation of SRF induction post-DHT. Moreover, DHT stimulation failed to induce SRF transcriptional activity in AR-negative PC346 DCC cells, which was only restored following AR over-expression. Next, SRF expression was down-regulated by siRNA, resulting in AR increased transcriptional activity in castrate-resistant LNCaP Abl cells but not in the parental LNCaP. This negative feedback loop in the resistant cells was confirmed by immunohistochemistry which showed a negative correlation between AR and SRF expression in CRPC bone metastases and a positive correlation in androgen-naïve prostatectomies. Cell proliferation was next assessed following SRF inhibition, demonstrating that SRF inhibition is more effective than AR inhibition in castrate-resistant cells.
  
  
  CONCLUSIONS
  Our data support SRF as a promising therapeutic target in combination with current treatments.
authors.affiliation: UCDSchool of Medicine and Medical Science, Conway Institute of Biomolecular Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Maria
authors.initials: M
authors.lastname: Prencipe
authors.affiliation: UCDSchool of Medicine and Medical Science, Conway Institute of Biomolecular Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: Amanda
authors.initials: A
authors.lastname: O'Neill
authors.affiliation: OncoMark Limited, NovaUCD, Belfield Innovation Park, Dublin, Ireland.
authors.forename: Gillian
authors.initials: G
authors.lastname: O'Hurley
authors.affiliation: Systems Biology Ireland, University College Dublin, Dublin, Ireland.
authors.forename: Lan K
authors.initials: LK
authors.lastname: Nguyen
authors.affiliation: Department of Pathology, St Vincent's University Hospital, Dublin, Ireland.
authors.forename: Aurelie
authors.initials: A
authors.lastname: Fabre
authors.affiliation: Department of Urology, Sk, å, ne University Hospital, Malm, ö, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Bjartell
authors.affiliation: OncoMark Limited, NovaUCD, Belfield Innovation Park, Dublin, Ireland.|UCD School of Biomolecular and Biomedical Science, Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: William M
authors.initials: WM
authors.lastname: Gallagher
authors.affiliation: Department of Urology, University of Washington, Seattle, Washington, USA.
authors.forename: Colm
authors.initials: C
authors.lastname: Morrissey
authors.affiliation: Department of Pathology, RCSI Education and Research Centre, Beaumont Hospital, Dublin, Ireland.
authors.forename: Elaine W
authors.initials: EW
authors.lastname: Kay
authors.affiliation: UCDSchool of Medicine and Medical Science, Conway Institute of Biomolecular Biomedical Research, University College Dublin, Dublin, Ireland.
authors.forename: R William
authors.initials: RW
authors.lastname: Watson
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology*; D013196:Dihydrotestosterone / Q000494:pharmacology; D015536:Down-Regulation; D006801:Humans; D008297:Male; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D034741:RNA, Small Interfering; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D026362:Serum Response Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D011944:Receptors, Androgen; D026362:Serum Response Factor; D013196:Dihydrotestosterone
keywords: androgen receptor; castrate-resistant prostate cancer; serum response factor