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Stat3 is required for anchorage‐independent growth and metastasis but not for mammary tumor development downstream of the ErbB‐2 oncogene
Author(s) -
Barbieri Isaia,
Quaglino Elena,
Maritano Diego,
Pannellini Tania,
Riera Ludovica,
Cavallo Federica,
Forni Guido,
Musiani Piero,
Chiarle Roberto,
Poli Valeria
Publication year - 2010
Publication title -
molecular carcinogenesis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.254
H-Index - 97
eISSN - 1098-2744
pISSN - 0899-1987
DOI - 10.1002/mc.20605
Subject(s) - stat3 , biology , oncogene , cancer research , stat protein , erbb , carcinogenesis , gene silencing , small hairpin rna , mammary gland , metastasis , transcription factor , cell culture , signal transduction , breast cancer , cell , cancer , gene knockdown , cell cycle , microbiology and biotechnology , gene , biochemistry , genetics
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. © 2009 Wiley‐Liss, Inc.