PMID- 11010820
OWN - NLM
STAT- MEDLINE
DCOM- 20001113
LR  - 20191210
IS  - 0014-4827 (Print)
IS  - 0014-4827 (Linking)
VI  - 260
IP  - 1
DP  - 2000 Oct 10
TI  - Effects of antiandrogens on chromatin remodeling and transcription of the 
      integrated mouse mammary tumor virus promoter.
PG  - 160-5
AB  - Inhibition of the ligand-activated androgen receptor (AR) by antiandrogens plays 
      an important role in the treatment of various hyperandrogenic disorders including 
      prostate cancer. However, the molecular mechanisms of antiandrogen activity in 
      vivo remain unclear. In this study we analyzed the effects of cyproterone acetate 
      (CPA), flutamide (F), and hydroxyflutamide (OHF) on transcriptional activation 
      and chromatin remodeling of the genomically integrated mouse mammary tumor virus 
      (MMTV) promoter. This promoter has provided an excellent model system to study 
      the impact of steroid hormones on transcriptional activation in the context of a 
      defined chromatin structure. The MMTV hormone response element is positioned on a 
      phased nucleosome, which becomes remodeled in response to steroids. We utilized 
      this model system in mouse L-cell fibroblasts that contain a stably integrated 
      MMTV promoter. In these cells, dihydrotestosterone (DHT) induced a large increase 
      of AR protein levels that correlated with transcriptional activation and 
      chromatin remodeling of the MMTV promoter. Coadministration of DHT and CPA or DHT 
      and OHF in these cells inhibited the increase of AR levels, which resulted in a 
      strong blockage of transcriptional activation and chromatin remodeling of the 
      MMTV promoter. In contrast, F had no significant influence on these activities. 
      We conclude that a major portion of the antiandrogenic effects of CPA and OHF in 
      vivo are mediated by the reduction of AR levels.
CI  - Copyright 2000 Academic Press.
FAU - List, H J
AU  - List HJ
AD  - Departments of Oncology, Georgetown University, Washington, D.C 20007, USA.
FAU - Smith, C L
AU  - Smith CL
FAU - Martinez, E
AU  - Martinez E
FAU - Harris, V K
AU  - Harris VK
FAU - Danielsen, M
AU  - Danielsen M
FAU - Riegel, A T
AU  - Riegel AT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Exp Cell Res
JT  - Experimental cell research
JID - 0373226
RN  - 0 (Androgen Antagonists)
RN  - 0 (Chromatin)
RN  - 0 (DNA Probes)
RN  - 0 (Receptors, Androgen)
RN  - 31D90UKP5Y (hydroxyflutamide)
RN  - 4KM2BN5JHF (Cyproterone Acetate)
RN  - 76W6J0943E (Flutamide)
SB  - IM
MH  - Androgen Antagonists/*pharmacology
MH  - Animals
MH  - Base Sequence
MH  - Chromatin/*drug effects
MH  - Cyproterone Acetate/pharmacology
MH  - DNA Probes/genetics
MH  - Female
MH  - Flutamide/analogs & derivatives/pharmacology
MH  - L Cells
MH  - Male
MH  - Mammary Tumor Virus, Mouse/*drug effects/*genetics
MH  - Mice
MH  - Promoter Regions, Genetic/*drug effects
MH  - Receptors, Androgen/drug effects/metabolism
MH  - Transcriptional Activation/drug effects
EDAT- 2000/09/30 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/09/30 11:00
PHST- 2000/09/30 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/09/30 11:00 [entrez]
AID - S0014-4827(00)95018-3 [pii]
AID - 10.1006/excr.2000.5018 [doi]
PST - ppublish
SO  - Exp Cell Res. 2000 Oct 10;260(1):160-5. doi: 10.1006/excr.2000.5018.