Stat3 Is Required for Anchorage-Independent Growth and Metastasis But Not for Mammary Tumor Development Downstream of the ErbB-2 Oncogene

被引:27
作者
Barbieri, Isaia [1 ,2 ]
Quaglino, Elena [1 ,3 ]
Maritano, Diego [2 ]
Pannellini, Tania [4 ]
Riera, Ludovica [5 ]
Cavallo, Federica [1 ,3 ]
Forni, Guido [1 ,3 ]
Musiani, Piero [4 ]
Chiarle, Roberto [5 ]
Poli, Valeria [1 ,2 ]
机构
[1] Univ Turin, Ctr Mol Biotechnol, I-10126 Turin, Italy
[2] Univ Turin, Dept Genet Biol & Biochem, I-10126 Turin, Italy
[3] Univ Turin, Dept Clin & Biol Sci, I-10126 Turin, Italy
[4] Univ G dAnnunzio, Ageing Res Ctr CeSI, Chieti, Italy
[5] San Giovanni Battista Hosp, CERMS, Turin, Italy
关键词
neu; conditional mutagenesis; breast tumors; transgenic mice; TRANSGENIC MICE; BREAST-CANCER; EPITHELIAL-CELLS; ACTIVATION; EXPRESSION; CARCINOGENESIS; KINASE; TARGET; LINES; ADENOCARCINOMAS;
D O I
10.1002/mc.20605
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The oncogenic transcription factor Stat3 is constitutively active in a high percentage of human tumors including mammary adenocarcinomas and is reported to participate in the ErbB-2 oncogene signaling. In order to assess the role of signal transducer and activator of transcription 3 (Stat3) in mammary tumorigenesis downstream of ErbB-2, we generated mice expressing the activated rat ErbB-2 (neu) but lacking Stat3 in the mammary epithelium. Stat3 is apparently not required for neu-driven mammary tumorigenesis as tumors developed similarly in both Stat3-sufficient and Stat3-deficient glands. However, short hairpin RNA (shRNA)-mediated Stat3 silencing in a neu-overexpressing tumor-derived cell line completely abolished both neu-driven anchorage-independent growth and lung metastasis. Our data suggest that Stat3 might be a useful therapeutic target in breast tumors showing amplification and/or overexpression of the ErbB-2 oncogene, which normally display aggressive, metastatic behavior. (C) 2009 Wiley-Liss, Inc.
引用
收藏
页码:114 / 120
页数:7
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