PMID- 18320593
OWN - NLM
STAT- MEDLINE
DCOM- 20081017
LR  - 20131121
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 104
IP  - 5
DP  - 2008 Aug 1
TI  - 5alpha-androstane-3alpha,17beta-diol supports human prostate cancer cell survival 
      and proliferation through androgen receptor-independent signaling pathways: 
      implication of androgen-independent prostate cancer progression.
PG  - 1612-24
LID - 10.1002/jcb.21731 [doi]
AB  - Androgen and androgen receptor (AR) are involved in growth of normal prostate and 
      development of prostatic diseases including prostate cancer. Androgen deprivation 
      therapy is used for treating advanced prostate cancer. This therapeutic approach 
      focuses on suppressing the accumulation of potent androgens, testosterone and 
      5alpha-dihydrotestosterone (5alpha-DHT), or inactivating the AR. Unfortunately, 
      the majority of patients with prostate cancer eventually advance to 
      androgen-independent states and no longer respond to the therapy. In addition to 
      the potent androgens, 5alpha-androstane-3alpha,17beta-diol (3alpha-diol), reduced 
      from 5alpha-DHT through 3alpha-hydroxysteroid dehydrogenases (3alpha-HSDs), 
      activated signaling may represent a novel pathway responsible for the progression 
      to androgen-independent prostate cancer. Androgen sensitive human prostate cancer 
      LNCaP cells were used to compare 5alpha-DHT and 3alpha-diol activated androgenic 
      effects. In contrast to 5alpha-DHT, 3alpha-diol regulated unique patterns of 
      beta-catenin and Akt expression as well as Akt phosphorylation in parental and in 
      AR-silenced LNCaP cells. More significantly, 3alpha-diol, but not 5alpha-DHT, 
      supported AR-silenced LNCaP cells and AR negative prostate cancer PC-3 cell 
      proliferation. 3alpha-diol-activated androgenic effects in prostate cells cannot 
      be attributed to the accumulation of 5alpha-DHT, since 5alpha-DHT formation was 
      not detected following 3alpha-diol administration. Potential accumulation of 
      3alpha-diol, as a result of elevated 3alpha-HSD expression in cancerous prostate, 
      may continue to support prostate cancer growth in the presence of androgen 
      deprivation. Future therapeutic strategies for treating advanced prostate cancer 
      might need to target reductive 3alpha-HSD to block intraprostatic 3alpha-diol 
      accumulation.
FAU - Yang, Qing
AU  - Yang Q
AD  - Department of Urology, University of Oklahoma Health Sciences Center, Oklahoma 
      City, Oklahoma 73104, USA.
FAU - Titus, Mark A
AU  - Titus MA
FAU - Fung, Kar-Ming
AU  - Fung KM
FAU - Lin, Hsueh-Kung
AU  - Lin HK
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (AR protein, human)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, Androgen)
RN  - 0 (beta Catenin)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 25126-76-5 (Androstane-3,17-diol)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Androstane-3,17-diol/*pharmacology
MH  - Apoptosis/drug effects
MH  - Cell Line, Tumor
MH  - Cell Proliferation/drug effects
MH  - Cell Survival/drug effects
MH  - Cytoplasm/drug effects
MH  - Dihydrotestosterone/pharmacology
MH  - Disease Progression
MH  - Drug Screening Assays, Antitumor
MH  - Gene Expression Regulation, Neoplastic/drug effects
MH  - Genes, Neoplasm
MH  - Humans
MH  - Male
MH  - Models, Biological
MH  - Phosphorylation/drug effects
MH  - Prostatic Neoplasms/enzymology/genetics/*pathology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering/metabolism
MH  - Receptors, Androgen/metabolism
MH  - Signal Transduction/*drug effects
MH  - Time Factors
MH  - beta Catenin/metabolism
EDAT- 2008/03/06 09:00
MHDA- 2008/10/18 09:00
CRDT- 2008/03/06 09:00
PHST- 2008/03/06 09:00 [pubmed]
PHST- 2008/10/18 09:00 [medline]
PHST- 2008/03/06 09:00 [entrez]
AID - 10.1002/jcb.21731 [doi]
PST - ppublish
SO  - J Cell Biochem. 2008 Aug 1;104(5):1612-24. doi: 10.1002/jcb.21731.