PMID- 11596023
OWN - NLM
STAT- MEDLINE
DCOM- 20011204
LR  - 20190620
IS  - 0008-543X (Print)
IS  - 0008-543X (Linking)
VI  - 92
IP  - 8
DP  - 2001 Oct 15
TI  - CpG hypermethylation of the promoter region inactivates the estrogen 
      receptor-beta gene in patients with prostate carcinoma.
PG  - 2076-83
AB  - BACKGROUND: The down-regulation of the estrogen receptor-beta (ERbeta) gene is 
      associated with several malignancies, including prostate carcinoma. The purpose 
      of the current study was to investigate the mechanisms of ERbeta inactivation 
      through the analysis of CpG methylation of the promoter region of ERbeta gene. 
      METHODS: ERbeta protein expression was examined by immunohistochemistry in 23 
      cases of human prostate carcinoma and 40 cases of benign prostatic hyperplasia 
      (BPH). DNA was extracted from these tissues and processed for sodium bisulfite 
      genomic sequencing. The percentage of methylation of CpG sites in the promoter 
      region of ERbeta (-376 to -117), which contains 19 CpG sites, was determined from 
      genomic sequencing data. The prostate carcinoma cell lines DU145 and ND1 were 
      treated with the demethylating agent 5-AZAC and ERbeta mRNA expression was 
      analyzed by reverse transcriptase-polymerase chain reaction. RESULTS: In BPH 
      tissues, ERbeta protein expression was found mainly in epithelial cells. ERbeta 
      protein expression was lacking in 83% of prostate carcinoma samples (19 of 23 
      samples) whereas all cases of BPH (40 of 40) demonstrated expression of ERbeta 
      protein. The mechanism of inactivation of the ERbeta gene in prostate carcinoma 
      was CpG methylation because the degree of methylation at all CpG sites within the 
      promoter region between -376 and -117 was higher in prostate carcinoma samples 
      compared with BPH tissues. Nine of 19 CpG sites within the promoter region of 
      ERbeta displayed significant differences in methylation between prostate 
      carcinoma and BPH samples. The prostate carcinoma cell lines appeared to lack 
      ERbeta expression. However, 5-AZAC treatment restored ERbeta expression in those 
      cell lines, suggesting that methylation inactivates the ERbeta gene in prostate 
      carcinoma. CONCLUSIONS: The results of the current study demonstrate, for what we 
      believe to be the first time, that the inactivation of the ERbeta gene in 
      prostate carcinoma occurs through CpG methylation of the promoter region of this 
      gene.
CI  - Copyright 2001 American Cancer Society.
FAU - Nojima, D
AU  - Nojima D
AD  - Department of Urology, University of California-San Francisco and Veterans 
      Affairs Medical Center, San Francisco, California 94121, USA.
FAU - Li, L C
AU  - Li LC
FAU - Dharia, A
AU  - Dharia A
FAU - Perinchery, G
AU  - Perinchery G
FAU - Ribeiro-Filho, L
AU  - Ribeiro-Filho L
FAU - Yen, T S
AU  - Yen TS
FAU - Dahiya, R
AU  - Dahiya R
LA  - eng
GR  - CA64872/CA/NCI NIH HHS/United States
GR  - DK47517/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.
PL  - United States
TA  - Cancer
JT  - Cancer
JID - 0374236
RN  - 0 (Estrogen Receptor beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Estrogen)
RN  - 776B62CQ27 (Decitabine)
RN  - EC 2.1.1.- (DNA Modification Methylases)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Azacitidine/*analogs & derivatives/pharmacology
MH  - *DNA Methylation
MH  - DNA Modification Methylases/antagonists & inhibitors
MH  - Decitabine
MH  - Estrogen Receptor beta
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Male
MH  - Neoplasms, Hormone-Dependent/*genetics/metabolism/pathology
MH  - Promoter Regions, Genetic
MH  - Prostatic Hyperplasia/metabolism/pathology
MH  - Prostatic Neoplasms/*genetics/metabolism/pathology
MH  - RNA, Messenger/analysis
MH  - Receptors, Estrogen/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Tumor Cells, Cultured
EDAT- 2001/10/12 10:00
MHDA- 2002/01/05 10:01
CRDT- 2001/10/12 10:00
PHST- 2001/10/12 10:00 [pubmed]
PHST- 2002/01/05 10:01 [medline]
PHST- 2001/10/12 10:00 [entrez]
AID - 10.1002/1097-0142(20011015)92:8<2076::AID-CNCR1548>3.0.CO;2-A [pii]
AID - 10.1002/1097-0142(20011015)92:8<2076::aid-cncr1548>3.0.co;2-a [doi]
PST - ppublish
SO  - Cancer. 2001 Oct 15;92(8):2076-83. doi: 
      10.1002/1097-0142(20011015)92:8<2076::aid-cncr1548>3.0.co;2-a.