Interleukin-4 activates androgen receptor through CBP/p300

Soo Ok Lee, Jae Yeon Chun, Nagalakshmi Nadiminty, Wei Lou, Siting Feng, Allen C Gao

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

BACKGROUND. Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen-sensitive prostate cancer cells. However, the mechanism of IL-4 mediated AR activation has not yet been revealed. METHODS. The effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL-4 on the interactions of AR and CBP/p300 was examined by co-immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated AR activation. RESULTS. We found that IL-4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA. CONCLUSION. These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity.

Original languageEnglish (US)
Pages (from-to)126-132
Number of pages7
JournalProstate
Volume69
Issue number2
DOIs
StatePublished - Feb 1 2009

Fingerprint

Androgen Receptors
Interleukin-4
p300-CBP Transcription Factors
Androgens
Small Interfering RNA
Prostatic Neoplasms
Castration
Acetylation
Histone Acetyltransferases
Immunoprecipitation
Down-Regulation
Western Blotting

Keywords

  • AR
  • CBP/p300
  • Interleukin-4
  • Prostate cancer

ASJC Scopus subject areas

  • Urology
  • Oncology
  • Medicine(all)

Cite this

Lee, S. O., Chun, J. Y., Nadiminty, N., Lou, W., Feng, S., & Gao, A. C. (2009). Interleukin-4 activates androgen receptor through CBP/p300. Prostate, 69(2), 126-132. https://doi.org/10.1002/pros.20865

Interleukin-4 activates androgen receptor through CBP/p300. / Lee, Soo Ok; Chun, Jae Yeon; Nadiminty, Nagalakshmi; Lou, Wei; Feng, Siting; Gao, Allen C.

In: Prostate, Vol. 69, No. 2, 01.02.2009, p. 126-132.

Research output: Contribution to journalArticle

Lee, SO, Chun, JY, Nadiminty, N, Lou, W, Feng, S & Gao, AC 2009, 'Interleukin-4 activates androgen receptor through CBP/p300', Prostate, vol. 69, no. 2, pp. 126-132. https://doi.org/10.1002/pros.20865
Lee SO, Chun JY, Nadiminty N, Lou W, Feng S, Gao AC. Interleukin-4 activates androgen receptor through CBP/p300. Prostate. 2009 Feb 1;69(2):126-132. https://doi.org/10.1002/pros.20865
Lee, Soo Ok ; Chun, Jae Yeon ; Nadiminty, Nagalakshmi ; Lou, Wei ; Feng, Siting ; Gao, Allen C. / Interleukin-4 activates androgen receptor through CBP/p300. In: Prostate. 2009 ; Vol. 69, No. 2. pp. 126-132.
@article{a2051a369f8c4641a6bc6149b0d5c476,
title = "Interleukin-4 activates androgen receptor through CBP/p300",
abstract = "BACKGROUND. Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen-sensitive prostate cancer cells. However, the mechanism of IL-4 mediated AR activation has not yet been revealed. METHODS. The effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL-4 on the interactions of AR and CBP/p300 was examined by co-immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated AR activation. RESULTS. We found that IL-4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA. CONCLUSION. These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity.",
keywords = "AR, CBP/p300, Interleukin-4, Prostate cancer",
author = "Lee, {Soo Ok} and Chun, {Jae Yeon} and Nagalakshmi Nadiminty and Wei Lou and Siting Feng and Gao, {Allen C}",
year = "2009",
month = "2",
day = "1",
doi = "10.1002/pros.20865",
language = "English (US)",
volume = "69",
pages = "126--132",
journal = "Prostate",
issn = "0270-4137",
publisher = "Wiley-Liss Inc.",
number = "2",

}

TY - JOUR

T1 - Interleukin-4 activates androgen receptor through CBP/p300

AU - Lee, Soo Ok

AU - Chun, Jae Yeon

AU - Nadiminty, Nagalakshmi

AU - Lou, Wei

AU - Feng, Siting

AU - Gao, Allen C

PY - 2009/2/1

Y1 - 2009/2/1

N2 - BACKGROUND. Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen-sensitive prostate cancer cells. However, the mechanism of IL-4 mediated AR activation has not yet been revealed. METHODS. The effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL-4 on the interactions of AR and CBP/p300 was examined by co-immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated AR activation. RESULTS. We found that IL-4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA. CONCLUSION. These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity.

AB - BACKGROUND. Aberrant activation of androgen receptor (AR) plays an important role in the progression of castration resistant prostate cancer. Interleukin-4 (IL-4) enhances AR activation in the absence of androgen and stimulates castration resistant growth of androgen-sensitive prostate cancer cells. However, the mechanism of IL-4 mediated AR activation has not yet been revealed. METHODS. The effect of IL-4 on CBP/p300 expression was examined by Western blot analysis. The effect of IL-4 on the interactions of AR and CBP/p300 was examined by co-immunoprecipitation and ChIP assays. CBP/p300 siRNA was used to knockdown CBP/p300 expression to examine the role of CBP/p300 expression on IL-4 mediated AR activation. RESULTS. We found that IL-4 increases CBP/p300 protein expression and enhances interaction of AR with CBP/p300 proteins through an increase in the recruitment of CBP/p300 protein to the androgen responsive elements in the promoters of androgen responsive genes. Down regulation of CBP/p300 expression using CBP/p300 specific siRNA abolished IL-4 mediated AR activation, suggesting that CBP/p300 is responsible for AR activation induced by IL-4. Furthermore, AR activation can be enhanced by AR acetylation induced by IL-4 in prostate cancer cells. The IL-4 mediated AR acetylation can be blocked by knocking down CBP/p300 expression using CBP/p300 specific siRNA. CONCLUSION. These results suggest that IL-4 activates AR through enhanced expression of CBP/p300 and its histone acetyltransferase activity.

KW - AR

KW - CBP/p300

KW - Interleukin-4

KW - Prostate cancer

UR - http://www.scopus.com/inward/record.url?scp=58849116423&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58849116423&partnerID=8YFLogxK

U2 - 10.1002/pros.20865

DO - 10.1002/pros.20865

M3 - Article

VL - 69

SP - 126

EP - 132

JO - Prostate

JF - Prostate

SN - 0270-4137

IS - 2

ER -