PMID- 20133657
OWN - NLM
STAT- MEDLINE
DCOM- 20100510
LR  - 20211020
IS  - 1091-6490 (Electronic)
IS  - 0027-8424 (Print)
IS  - 0027-8424 (Linking)
VI  - 107
IP  - 7
DP  - 2010 Feb 16
TI  - Estrogen receptor-beta activated apoptosis in benign hyperplasia and cancer of 
      the prostate is androgen independent and TNFalpha mediated.
PG  - 3123-8
LID - 10.1073/pnas.0905524107 [doi]
AB  - Prostate cancer (PCa) and benign prostatic hyperplasia (BPH) are 
      androgen-dependent diseases commonly treated by inhibiting androgen action. 
      However, androgen ablation or castration fail to target androgen-independent 
      cells implicated in disease etiology and recurrence. Mechanistically different to 
      castration, this study shows beneficial proapoptotic actions of estrogen 
      receptor-beta (ERbeta) in BPH and PCa. ERbeta agonist induces apoptosis in 
      prostatic stromal, luminal and castrate-resistant basal epithelial cells of 
      estrogen-deficient aromatase knock-out mice. This occurs via extrinsic 
      (caspase-8) pathways, without reducing serum hormones, and perturbs the 
      regenerative capacity of the epithelium. TNFalpha knock-out mice fail to respond 
      to ERbeta agonist, demonstrating the requirement for TNFalpha signaling. In human 
      tissues, ERbeta agonist induces apoptosis in stroma and epithelium of xenografted 
      BPH specimens, including in the CD133(+) enriched putative stem/progenitor cells 
      isolated from BPH-1 cells in vitro. In PCa, ERbeta causes apoptosis in Gleason 
      Grade 7 xenografted tissues and androgen-independent cells lines (PC3 and DU145) 
      via caspase-8. These data provide evidence of the beneficial effects of ERbeta 
      agonist on epithelium and stroma of BPH, as well as androgen-independent tumor 
      cells implicated in recurrent disease. Our data are indicative of the therapeutic 
      potential of ERbeta agonist for treatment of PCa and/or BPH with or without 
      androgen withdrawal.
FAU - McPherson, Stephen J
AU  - McPherson SJ
AD  - Prostate and Breast Cancer Research Group, Department of Anatomy and 
      Developmental Biology, Monash University, Clayton, Victoria 3800, Australia.
FAU - Hussain, Shirin
AU  - Hussain S
FAU - Balanathan, Preetika
AU  - Balanathan P
FAU - Hedwards, Shelley L
AU  - Hedwards SL
FAU - Niranjan, Birunthi
AU  - Niranjan B
FAU - Grant, Michael
AU  - Grant M
FAU - Chandrasiri, Upeksha P
AU  - Chandrasiri UP
FAU - Toivanen, Roxanne
AU  - Toivanen R
FAU - Wang, Yuzhuo
AU  - Wang Y
FAU - Taylor, Renea A
AU  - Taylor RA
FAU - Risbridger, Gail P
AU  - Risbridger GP
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20100201
PL  - United States
TA  - Proc Natl Acad Sci U S A
JT  - Proceedings of the National Academy of Sciences of the United States of America
JID - 7505876
RN  - 0 (Androgens)
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (Tumor Necrosis Factor-alpha)
SB  - IM
MH  - Analysis of Variance
MH  - Androgens/metabolism
MH  - Animals
MH  - Apoptosis/*physiology
MH  - Cell Line, Tumor
MH  - Estrogen Receptor beta/agonists/*metabolism
MH  - Gene Expression Profiling
MH  - Humans
MH  - Hyperplasia/*metabolism
MH  - Immunohistochemistry
MH  - Male
MH  - Mice
MH  - Mice, Knockout
MH  - Prostate/metabolism/*pathology
MH  - Prostatic Neoplasms/*metabolism
MH  - Tumor Necrosis Factor-alpha/genetics/*metabolism
PMC - PMC2840300
COIS- The authors declare no conflict of interest.
EDAT- 2010/02/06 06:00
MHDA- 2010/05/11 06:00
PMCR- 2010/02/01
CRDT- 2010/02/06 06:00
PHST- 2010/02/06 06:00 [entrez]
PHST- 2010/02/06 06:00 [pubmed]
PHST- 2010/05/11 06:00 [medline]
PHST- 2010/02/01 00:00 [pmc-release]
AID - 0905524107 [pii]
AID - 200905524 [pii]
AID - 10.1073/pnas.0905524107 [doi]
PST - ppublish
SO  - Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3123-8. doi: 
      10.1073/pnas.0905524107. Epub 2010 Feb 1.