PMID- 26816736
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20160128
LR  - 20201001
IS  - 2223-4691 (Print)
IS  - 2223-4691 (Electronic)
IS  - 2223-4683 (Linking)
VI  - 2
IP  - 3
DP  - 2013 Sep
TI  - Androgen receptor-mediated non-genomic regulation of prostate cancer cell 
      proliferation.
PG  - 187-96
LID - 10.3978/j.issn.2223-4683.2013.09.07 [doi]
AB  - Androgen receptor (AR)-mediated signaling is necessary for prostate cancer cell 
      proliferation and an important target for therapeutic drug development. 
      Canonically, AR signals through a genomic or transcriptional pathway, involving 
      the translocation of androgen-bound AR to the nucleus, its binding to cognate 
      androgen response elements on promoter, with ensuing modulation of target gene 
      expression, leading to cell proliferation. However, prostate cancer cells can 
      show dose-dependent proliferation responses to androgen within minutes, without 
      the need for genomic AR signaling. This proliferation response known as the 
      non-genomic AR signaling is mediated by cytoplasmic AR, which facilitates the 
      activation of kinase-signaling cascades, including the Ras-Raf-1, 
      phosphatidyl-inositol 3-kinase (PI3K)/Akt and protein kinase C (PKC), which in 
      turn converge on mitogen-activated protein kinase (MAPK)/extracellular 
      signal-regulated kinase (ERK) activation, leading to cell proliferation. Further, 
      since activated ERK may also phosphorylate AR and its coactivators, the 
      non-genomic AR signaling may enhance AR genomic activity. Non-genomic AR 
      signaling may occur in an ERK-independent manner, via activation of mammalian 
      target of rapamycin (mTOR) pathway, or modulation of intracellular Ca(2+) 
      concentration through plasma membrane G protein-coupled receptors (GPCRs). These 
      data suggest that therapeutic strategies aimed at preventing AR nuclear 
      translocation and genomic AR signaling alone may not completely abrogate AR 
      signaling. Thus, elucidation of mechanisms that underlie non-genomic AR signaling 
      may identify potential mechanisms of resistance to current anti-androgens and 
      help developing novel therapies that abolish all AR signaling in prostate cancer.
FAU - Liao, Ross S
AU  - Liao RS
AD  - Department of Urology, University of Texas Southwestern Medical Center at Dallas, 
      Dallas, Texas 75390, USA.
FAU - Ma, Shihong
AU  - Ma S
AD  - Department of Urology, University of Texas Southwestern Medical Center at Dallas, 
      Dallas, Texas 75390, USA.
FAU - Miao, Lu
AU  - Miao L
AD  - Department of Urology, University of Texas Southwestern Medical Center at Dallas, 
      Dallas, Texas 75390, USA.
FAU - Li, Rui
AU  - Li R
AD  - Department of Urology, University of Texas Southwestern Medical Center at Dallas, 
      Dallas, Texas 75390, USA.
FAU - Yin, Yi
AU  - Yin Y
AD  - Department of Urology, University of Texas Southwestern Medical Center at Dallas, 
      Dallas, Texas 75390, USA.
FAU - Raj, Ganesh V
AU  - Raj GV
AD  - Department of Urology, University of Texas Southwestern Medical Center at Dallas, 
      Dallas, Texas 75390, USA.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - China
TA  - Transl Androl Urol
JT  - Translational andrology and urology
JID - 101581119
PMC - PMC4708176
OTO - NOTNLM
OT  - Androgen receptor (AR)
OT  - ERK MAP kinases
OT  - cell proliferation
OT  - non-genomic signaling
OT  - prostate cancer
COIS- Conflicts of Interest: The authors have no conflicts of interest to declare.
EDAT- 2013/09/01 00:00
MHDA- 2013/09/01 00:01
PMCR- 2013/09/01
CRDT- 2016/01/28 06:00
PHST- 2016/01/28 06:00 [entrez]
PHST- 2013/09/01 00:00 [pubmed]
PHST- 2013/09/01 00:01 [medline]
PHST- 2013/09/01 00:00 [pmc-release]
AID - tau-02-03-187 [pii]
AID - 10.3978/j.issn.2223-4683.2013.09.07 [doi]
PST - ppublish
SO  - Transl Androl Urol. 2013 Sep;2(3):187-96. doi: 
      10.3978/j.issn.2223-4683.2013.09.07.