The androgen receptor cistrome is extensively reprogrammed in human prostate tumorigenesis

被引：299

作者：

Pomerantz, Mark M. ^{[1
,2
]}

Li, Fugen ^{[3
,4
]}

Takeda, David Y. ^{[1
,2
,5
]}

Lenci, Romina ^{[1
,2
]}

Chonkar, Apurva ^{[1
,2
]}

Chabot, Matthew ^{[1
,2
]}

Cejas, Paloma ^{[1
,2
,3
]}

Vazquez, Francisca ^{[5
]}

Cook, Jennifer ^{[1
,2
]}

Shivdasani, Ramesh A. ^{[1
,2
,3
]}

Bowden, Michaela ^{[2
,6
]}

Lis, Rosina ^{[2
,6
]}

Hahn, William C. ^{[1
,2
,5
]}

Kantoff, Philip W. ^{[1
,2
]}

Brown, Myles ^{[1
,2
,3
]}

Loda, Massimo ^{[1
,2
,5
,6
]}

Long, Henry W. ^{[1
,2
,3
]}

Freedman, Matthew L. ^{[1
,2
,3
,5
]}

机构：

[1] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA

[2] Harvard Univ, Sch Med, Boston, MA USA

[3] Dana Farber Canc Inst, Ctr Funct Canc Epigenet, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Dept Biostat & Computat Biol, Boston, MA 02115 USA

[5] Eli & Edythe L Broad Inst, Cambridge, MA USA

[6] Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA

来源：

NATURE GENETICS | 2015年 / 47卷 / 11期

基金：

美国国家卫生研究院;

关键词：

TRANSCRIPTIONAL PROGRAM; CANCER; GENE; HOXB13; EXPRESSION; DIFFERENTIATION; MUTATIONS; ENHANCERS; ELEMENTS; FOXA1;

D O I：

10.1038/ng.3419

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells(1,2). The genome-wide map of these transcription factor binding sites has been termed the cistrome(3). Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13 colocalized at the reprogrammed AR binding sites in human tumor tissue. Introduction of FOXA1 and HOXB13 into an immortalized prostate cell line reprogrammed the AR cistrome to resemble that of a prostate tumor, functionally linking these specific factors to AR cistrome reprogramming. These findings offer mechanistic insights into a key set of events that drive normal prostate epithelium toward transformation and establish the centrality of epigenetic reprogramming in human prostate tumorigenesis.

引用

页码：1346 / +

页数：9

共 36 条

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