ZNF703 is a common Luminal B breast cancer oncogene that differentially regulates luminal and basal progenitors in human mammary epithelium

被引：114

作者：

Holland, Daniel G. ^{[1
,2
]}

Burleigh, Angela ^{[3
,4
]}

Git, Anna ^{[1
,2
]}

Goldgraben, Mae A. ^{[1
,2
]}

Perez-Mancera, Pedro A. ^{[1
,2
]}

Chin, Suet-Feung ^{[1
]}

Hurtado, Antonio ^{[1
]}

Bruna, Alejandro ^{[1
,2
]}

Ali, H. Raza ^{[1
,2
]}

Greenwood, Wendy ^{[1
,2
]}

Dunning, Mark J. ^{[1
]}

Samarajiwa, Shamith ^{[1
]}

Menon, Suraj ^{[1
]}

Rueda, Oscar M. ^{[1
,2
]}

Lynch, Andy G. ^{[1
]}

McKinney, Steven ^{[3
,4
]}

Ellis, Ian O. ^{[5
]}

Eaves, Connie J. ^{[3
,4
]}

Carroll, Jason S. ^{[1
,2
]}

Curtis, Christina ^{[1
,8
]}

Aparicio, Samuel ^{[3
,4
]}

Caldas, Carlos ^{[1
,2
,6
,7
]}

机构：

[1] Canc Res UK, Cambridge Res Inst, Cambridge, England

[2] Univ Cambridge, Dept Oncol, Li Ka Shing Ctr, Cambridge, England

[3] Univ British Columbia, Dept Pathol, Vancouver, BC, Canada

[4] BC Canc Agcy, Vancouver, BC, Canada

[5] Nottingham Univ Hosp NHS Trust, City Hosp Nottingham, Dept Histopathol, Nottingham, England

[6] Cambridge Univ Hosp NHS Fdn Trust, NIHR Cambridge Biomed Res Ctr, Cambridge, England

[7] Cambridge Univ Hosp NHS Fdn Trust, Cambridge Expt Canc Med Ctr, Cambridge, England

[8] Univ So Calif, Keck Sch Med, Dept Prevent Med, Los Angeles, CA USA

来源：

EMBO MOLECULAR MEDICINE | 2011年 / 3卷 / 03期

关键词：

breast cancer; oestrogen metabolism; Luminal B; oncogene; ZNF703; GENE; EXPRESSION; CELLS; FAMILY; PROTEINS; AMPLICON; SUBTYPES; TISSUE; TUMORS; HTERT;

D O I：

10.1002/emmm.201100122

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

The telomeric amplicon at 8p12 is common in oestrogen receptor-positive (ER+) breast cancers. Array-CGH and expression analyses of 1172 primary breast tumours revealed that ZNF703 was the single gene within the minimal amplicon and was amplified predominantly in the Luminal B subtype. Amplification was shown to correlate with increased gene and protein expression and was associated with a distinct expression signature and poor clinical outcome. ZNF703 transformed NIH 3T3 fibroblasts, behaving as a classical oncogene, and regulated proliferation in human luminal breast cancer cell lines and immortalized human mammary epithelial cells. Manipulation of ZNF703 expression in the luminal MCF7 cell line modified the effects of TGF beta on proliferation. Overexpression of ZNF703 in normal human breast epithelial cells enhanced the frequency of in vitro colony-forming cells from luminal progenitors. Taken together, these data strongly point to ZNF703 as a novel oncogene in Luminal B breast cancer.

引用

页码：167 / 180

页数：14

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