An Activated ErbB3/NRG1 Autocrine Loop Supports In Vivo Proliferation in Ovarian Cancer Cells

被引：197

作者：

Sheng, Qing ^{[1
,3
]}

Liu, Xinggang ^{[1
,3
]}

Fleming, Eleanor ^{[1
,3
]}

Yuan, Karen ^{[1
,3
]}

Piao, Huiying ^{[2
,3
,4
]}

Chen, Jinyun ^{[6
]}

Moustafa, Zeinab ^{[6
]}

Thomas, Roman K. ^{[7
,8
,9
,10
,11
]}

Greulich, Heidi ^{[2
,3
,5
,12
,13
]}

Schinzel, Anna ^{[2
,3
,12
,13
]}

Zaghlul, Sara ^{[1
,3
]}

Batt, David ^{[6
]}

Ettenberg, Seth ^{[6
]}

Meyerson, Matthew ^{[2
,3
,12
,13
]}

Schoeberl, Birgit ^{[14
]}

Kung, Andrew L. ^{[3
,15
,16
]}

Hahn, William C. ^{[2
,3
,12
,13
]}

Drapkin, Ronny ^{[2
,3
,4
]}

Livingston, David M. ^{[1
,3
]}

Liu, Joyce F. ^{[1
,2
,3
]}

机构：

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

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

[3] Harvard Univ, Sch Med, Boston, MA 02115 USA

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

[5] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[6] Novartis Oncol, Cambridge, MA 02139 USA

[7] Univ Cologne, Fac Med, D-50931 Cologne, Germany

[8] Univ Cologne, Max Planck Soc, Max Planck Inst Neurol Res, Klaus Joachim Zulch Labs, D-50931 Cologne, Germany

[9] Univ Cologne, Dept Internal Med 1, D-50937 Cologne, Germany

[10] Univ Cologne, Ctr Integrated Oncol, D-50937 Cologne, Germany

[11] Max Planck Soc, Chem Genom Ctr, D-44227 Dortmund, Germany

[12] MIT, Cambridge, MA 02142 USA

[13] Harvard Univ, Broad Inst, Cambridge, MA 02142 USA

[14] Merrimack Pharmaceut, Cambridge, MA 02139 USA

[15] Childrens Hosp, Boston, MA 02115 USA

[16] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02115 USA

来源：

CANCER CELL | 2010年 / 17卷 / 03期

关键词：

EPIDERMAL-GROWTH-FACTOR; PHASE-II TRIAL; ONCOGENE ADDICTION; PHOSPHATIDYLINOSITOL; 3-KINASE; MONOCLONAL-ANTIBODY; LUNG-CANCER; EXPRESSION; RECEPTOR; THERAPY; CARCINOMA;

D O I：

10.1016/j.ccr.2009.12.047

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ovarian cancer is a leading cause of death from gynecologic malignancies. Treatment for advanced-stage disease remains limited and, to date, targeted therapies have been incompletely explored. By systematically suppressing each human tyrosine kinase in ovarian cancer cell lines by RNAi, we found that an autocrine signal-transducing loop involving NRG1 and activated ErbB3 operates in a subset of primary ovarian cancers and ovarian cancer cell lines. Perturbation of this circuit with ErbB3-directed RNAi decreased cell growth in three-dimensional culture and resulted in decreased disease progression and prolonged survival in a xenograft mouse model of ovarian cancer. Furthermore, a monoclonal ErbB3-directed antibody (MM-121) also significantly inhibited tumor growth in vivo. These findings identify ErbB3 as a potential therapeutic target in ovarian cancer.

引用

页码：298 / 310

页数：13

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