Relationship Between Serum Response Factor and Androgen Receptor in Prostate Cancer
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8195263
- author
- 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
- organization
- publishing date
- 2015
- 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 Inc.
- 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
- 2016-04-01 10:20:04
- date last changed
- 2022-03-12 04:49:54
@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}},
keywords = {{castrate-resistant prostate cancer; serum response factor; androgen; receptor}},
language = {{eng}},
number = {{15}},
pages = {{1704--1717}},
publisher = {{John Wiley & Sons Inc.}},
series = {{The Prostate}},
title = {{Relationship Between Serum Response Factor and Androgen Receptor in Prostate Cancer}},
url = {{http://dx.doi.org/10.1002/pros.23051}},
doi = {{10.1002/pros.23051}},
volume = {{75}},
year = {{2015}},
}