PMID- 11923541
OWN - NLM
STAT- MEDLINE
DCOM- 20020422
LR  - 20220812
IS  - 1095-9203 (Electronic)
IS  - 0036-8075 (Linking)
VI  - 295
IP  - 5564
DP  - 2002 Mar 29
TI  - Molecular determinants for the tissue specificity of SERMs.
PG  - 2465-8
AB  - Selective estrogen receptor modulators (SERMs) mimic estrogen action in certain 
      tissues while opposing it in others. The therapeutic effectiveness of SERMs such 
      as tamoxifen and raloxifene in breast cancer depends on their antiestrogenic 
      activity. In the uterus, however, tamoxifen is estrogenic. Here, we show that 
      both tamoxifen and raloxifene induce the recruitment of corepressors to target 
      gene promoters in mammary cells. In endometrial cells, tamoxifen, but not 
      raloxifene, acts like estrogen by stimulating the recruitment of coactivators to 
      a subset of genes. The estrogen-like activity of tamoxifen in the uterus requires 
      a high level of steroid receptor coactivator 1 (SRC-1) expression. Thus cell 
      type- and promoter-specific differences in coregulator recruitment determine the 
      cellular response to SERMs.
FAU - Shang, Yongfeng
AU  - Shang Y
AD  - Department of Adult Oncology, Dana-Farber Cancer Institute, 44 Binney Street, and 
      Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 
      Boston, MA 02115, USA.
FAU - Brown, Myles
AU  - Brown M
LA  - eng
GR  - CA57374/CA/NCI 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  - Science
JT  - Science (New York, N.Y.)
JID - 0404511
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Repressor Proteins)
RN  - 0 (Selective Estrogen Receptor Modulators)
RN  - 0 (Transcription Factors)
RN  - 094ZI81Y45 (Tamoxifen)
RN  - 4F86W47BR6 (Raloxifene Hydrochloride)
RN  - 4TI98Z838E (Estradiol)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
RN  - EC 2.3.1.48 (Histone Acetyltransferases)
RN  - EC 2.3.1.48 (NCOA1 protein, human)
RN  - EC 2.3.1.48 (Nuclear Receptor Coactivator 1)
RN  - EC 3.5.1.98 (Histone Deacetylases)
SB  - IM
CIN - Science. 2002 Mar 29;295(5564):2380-1. PMID: 11923515
MH  - Breast/*drug effects/metabolism
MH  - Breast Neoplasms/genetics/metabolism
MH  - Cell Cycle
MH  - DNA-Binding Proteins/metabolism
MH  - Endometrial Neoplasms/genetics/metabolism
MH  - Endometrium/*drug effects/metabolism
MH  - Estradiol/pharmacology
MH  - Female
MH  - Gene Expression Regulation/drug effects
MH  - Gene Silencing
MH  - Genes, myc
MH  - Histone Acetyltransferases
MH  - Histone Deacetylases/metabolism
MH  - Humans
MH  - Insulin-Like Growth Factor I/genetics
MH  - Nuclear Receptor Coactivator 1
MH  - Organ Specificity
MH  - Promoter Regions, Genetic
MH  - Raloxifene Hydrochloride/metabolism/*pharmacology
MH  - Receptors, Estrogen/chemistry/metabolism
MH  - Repressor Proteins/metabolism
MH  - Response Elements
MH  - Selective Estrogen Receptor Modulators/metabolism/*pharmacology
MH  - Tamoxifen/metabolism/*pharmacology
MH  - Transcription Factors/genetics/*metabolism
MH  - Transcription, Genetic
MH  - Tumor Cells, Cultured
EDAT- 2002/03/30 10:00
MHDA- 2002/04/23 10:01
CRDT- 2002/03/30 10:00
PHST- 2002/03/30 10:00 [pubmed]
PHST- 2002/04/23 10:01 [medline]
PHST- 2002/03/30 10:00 [entrez]
AID - 295/5564/2465 [pii]
AID - 10.1126/science.1068537 [doi]
PST - ppublish
SO  - Science. 2002 Mar 29;295(5564):2465-8. doi: 10.1126/science.1068537.