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Relationship Between Serum Response Factor and Androgen Receptor in Prostate Cancer

Prencipe, Maria; O'Neill, Amanda; O'Hurley, Gillian; Nguyen, Lan K.; Fabre, Aurelie; Bjartell, Anders LU ; Gallagher, William M.; Morrissey, Colm; Kay, Elaine W. and Watson, R. William (2015) In The Prostate 75(15). p.1704-1717
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. MATERIALS AND 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... (More)
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. MATERIALS AND 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-naive prostatectomies. Cell proliferation was next assessed following SRF inhibition, demonstrating that SRF inhibition is more effective than AR inhibition in castrate-resistant cells. CONCLUSION. Our data support SRF as a promising therapeutic target in combination with current treatments. (C) 2015 Wiley Periodicals, Inc. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
castrate-resistant prostate cancer, serum response factor, androgen, receptor
in
The Prostate
volume
75
issue
15
pages
1704 - 1717
publisher
John Wiley & Sons
external identifiers
  • wos:000363219200004
  • scopus:84942817884
ISSN
0270-4137
DOI
10.1002/pros.23051
language
English
LU publication?
yes
id
fe5f6f18-4787-47ab-9d70-4681c57781c2 (old id 8195263)
date added to LUP
2015-11-26 10:43:44
date last changed
2017-03-19 03:08:33
@article{fe5f6f18-4787-47ab-9d70-4681c57781c2,
  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. MATERIALS AND 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-naive prostatectomies. Cell proliferation was next assessed following SRF inhibition, demonstrating that SRF inhibition is more effective than AR inhibition in castrate-resistant cells. CONCLUSION. Our data support SRF as a promising therapeutic target in combination with current treatments. (C) 2015 Wiley Periodicals, Inc.},
  author       = {Prencipe, Maria and O'Neill, Amanda and O'Hurley, Gillian and Nguyen, Lan K. and Fabre, Aurelie and Bjartell, Anders and Gallagher, William M. and Morrissey, Colm and Kay, Elaine W. and Watson, R. William},
  issn         = {0270-4137},
  keyword      = {castrate-resistant prostate cancer,serum response factor,androgen,receptor},
  language     = {eng},
  number       = {15},
  pages        = {1704--1717},
  publisher    = {John Wiley & Sons},
  series       = {The Prostate},
  title        = {Relationship Between Serum Response Factor and Androgen Receptor in Prostate Cancer},
  url          = {http://dx.doi.org/10.1002/pros.23051},
  volume       = {75},
  year         = {2015},
}