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

作者：Sheng Qing; Liu Xinggang; Fleming Eleanor; Yuan Karen; Piao Huiying; Chen Jinyun; Moustafa Zeinab; Thomas Roman K; Greulich Heidi; Schinzel Anna; Zaghlul Sara; Batt David; Ettenberg Seth; Meyerson Matthew; Schoeberl Birgit; Kung Andrew L; Hahn William C; Drapkin Ronny; Livingston David M^*; Liu Joyce F

来源：Cancer Cell, 2010, 17(3): 298-310.

DOI：10.1016/j.ccr.2009.12.047

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.

• 出版日期2010-3-16
• 单位MIT