Role of DNA methylation and histone acetylation in steroid receptor expression in breast cancer

被引:84
作者
Yan, L [1 ]
Yang, XW [1 ]
Davidson, NE [1 ]
机构
[1] Johns Hopkins Oncol Ctr, Baltimore, MD 21231 USA
关键词
breast cancer; DNA methylation; histone acetylation; steroid receptor;
D O I
10.1023/A:1011308707512
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
DNA methylation is an epigenetic modification that is associated with transcriptional silencing of gene expression in mammalian cells. Hypermethylation of the promoter CpG islands contributes to the loss of gene function of several tumor related genes, including estrogen receptor a (ER) and progesterone receptor (PR). Gene expression patterns are also heavily influenced by changes in chromatin structure during transcription. Indeed both the predominant mammalian DNA methyltransferase (DNMT1), and the histone deacetylases (HDACs) play crucial roles in maintaining transcriptionally repressive chromatin by forming suppressive complexes at replication foci. These new findings suggest that epigenetic changes might play a crucial role in gene inactivation in breast cancer. Further, inhibition of DNA methylation and histone deacetylation might be a therapeutic strategy in breast cancer, especially for those cancers with ER and PR negative phenotypes.
引用
收藏
页码:183 / 192
页数:10
相关论文
共 74 条
[1]   Genomic imprinting in mammals [J].
Bartolomei, MS ;
Tilghman, SM .
ANNUAL REVIEW OF GENETICS, 1997, 31 :493-525
[2]   DNA hypermethylation in tumorigenesis - epigenetics joins genetics [J].
Baylin, SB ;
Herman, JG .
TRENDS IN GENETICS, 2000, 16 (04) :168-174
[3]   Aberrant methylation of p16INK4a is an early event in lung cancer and a potential biomarker for early diagnosis [J].
Belinsky, SA ;
Nikula, KJ ;
Palmisano, WA ;
Michels, R ;
Saccomanno, G ;
Gabrielson, E ;
Baylin, SB ;
Herman, JG .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (20) :11891-11896
[4]   Gene silencing - Methylation meets acetylation [J].
Bestor, TH .
NATURE, 1998, 393 (6683) :311-312
[5]   CPG-RICH ISLANDS AND THE FUNCTION OF DNA METHYLATION [J].
BIRD, AP .
NATURE, 1986, 321 (6067) :209-213
[6]   Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer [J].
Cameron, EE ;
Bachman, KE ;
Myöhänen, S ;
Herman, JG ;
Baylin, SB .
NATURE GENETICS, 1999, 21 (01) :103-107
[7]  
Carducci MA, 1996, CLIN CANCER RES, V2, P379
[8]   TREATMENT OF SICKLE-CELL-ANEMIA WITH 5-AZACYTIDINE RESULTS IN INCREASED FETAL HEMOGLOBIN PRODUCTION AND IS ASSOCIATED WITH NONRANDOM HYPOMETHYLATION OF DNA AROUND THE GAMMA-DELTA-BETA-GLOBIN GENE-COMPLEX [J].
CHARACHE, S ;
DOVER, G ;
SMITH, K ;
TALBOT, CC ;
MOYER, M ;
BOYER, S .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1983, 80 (15) :4842-4846
[9]   ORAL SODIUM PHENYLBUTYRATE THERAPY IN HOMOZYGOUS BETA-THALASSEMIA - A CLINICAL-TRIAL [J].
COLLINS, AF ;
PEARSON, HA ;
GIARDINA, P ;
MCDONAGH, KT ;
BRUSILOW, SW ;
DOVER, GJ .
BLOOD, 1995, 85 (01) :43-49
[10]  
DOVER GJ, 1985, BLOOD, V66, P527