PMID- 12163482
OWN - NLM
STAT- MEDLINE
DCOM- 20021125
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 277
IP  - 41
DP  - 2002 Oct 11
TI  - Ligand-independent activation of the androgen receptor by interleukin-6 and the 
      role of steroid receptor coactivator-1 in prostate cancer cells.
PG  - 38087-94
AB  - The androgen receptor (AR) can be activated in the absence of androgens by 
      interleukin-6 (IL-6) in human prostate cancer cells. The events involved in 
      ligand-independent activation of the AR are unknown, but have been suggested to 
      involve phosphorylation of the AR itself or a receptor-associated protein. 
      Steroid receptor coactivator-1 (SRC-1) has been shown to interact with the human 
      AR and to modulate ligand-dependent AR transactivation and is regulated by 
      phosphorylation by MAPK. To date, no one has examined the role of SRC-1 in 
      ligand-independent activation of the AR by IL-6 or other signaling pathways known 
      to activate the full-length receptor. This study addressed this and has revealed 
      the following. 1) SRC-1 similarly enhanced ligand-independent activation of the 
      AR by IL-6 to the same magnitude as that obtained via ligand-dependent 
      activation. 2) Androgen and IL-6 stimulated the MAPK pathway. 3) MAPK was 
      required for both ligand-dependent and ligand-independent activation of the AR. 
      4) Phosphorylation of SRC-1 by MAPK was required for optimal ligand-independent 
      activation of the AR by IL-6. 5) Protein-protein interaction between endogenous 
      AR and SRC-1 was dependent upon treatment of LNCaP cells with IL-6 or R1881. 6) 
      Protein-protein interaction between the AR N-terminal domain and SRC-1 was 
      independent of MAPK. 7) Ligand-independent activation of the AR did not occur by 
      a mechanism of overexpression of either solely wild-type SRC-1 or mutant SRC-1 
      that mimics its phosphorylated form.
FAU - Ueda, Takeshi
AU  - Ueda T
AD  - Department of Cancer Endocrinology, British Columbia Cancer Agency, Vancouver, 
      British Columbia V5Z 4E6, Canada.
FAU - Mawji, Nasrin R
AU  - Mawji NR
FAU - Bruchovsky, Nicholas
AU  - Bruchovsky N
FAU - Sadar, Marianne D
AU  - Sadar MD
LA  - eng
GR  - P50 DK47656/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20020805
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Interleukin-6)
RN  - 0 (Ligands)
RN  - 0 (Receptors, Androgen)
RN  - 0 (Testosterone Congeners)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 2C323EGI97 (Metribolone)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
SB  - IM
MH  - Genes, Reporter
MH  - Histone Acetyltransferases
MH  - Humans
MH  - Interleukin-6/*metabolism
MH  - Ligands
MH  - MAP Kinase Signaling System/physiology
MH  - Male
MH  - Metribolone/metabolism
MH  - Mitogen-Activated Protein Kinases/metabolism
MH  - Nuclear Receptor Coactivator 1
MH  - Prostatic Neoplasms/*metabolism
MH  - Receptors, Androgen/genetics/*metabolism
MH  - Testosterone Congeners/metabolism
MH  - Trans-Activators/*metabolism
MH  - Transcription Factors/genetics/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2002/08/07 10:00
MHDA- 2002/11/26 04:00
CRDT- 2002/08/07 10:00
PHST- 2002/08/07 10:00 [pubmed]
PHST- 2002/11/26 04:00 [medline]
PHST- 2002/08/07 10:00 [entrez]
AID - S0021-9258(18)36283-5 [pii]
AID - 10.1074/jbc.M203313200 [doi]
PST - ppublish
SO  - J Biol Chem. 2002 Oct 11;277(41):38087-94. doi: 10.1074/jbc.M203313200. Epub 2002 
      Aug 5.