Stat3 is required for anchorage-independent growth and metastasis but not for mammary tumor development downstream of the ErbB-2 oncogene.
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.
Barbieri
Isaia
I
Molecular Biotechnology Center (MBC), University of Turin, 10126 Turin, Italy.
Quaglino
Elena
E
Maritano
Diego
D
Pannellini
Tania
T
Riera
Ludovica
L
Cavallo
Federica
F
Forni
Guido
G
Musiani
Piero
P
Chiarle
Roberto
R
Poli
Valeria
V
D000818:Animals; D001483:Base Sequence; D002448:Cell Adhesion / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D045744:Cell Line, Tumor; D017931:DNA Primers; D005260:Female; D020868:Gene Silencing; D018734:Genes, erbB-2; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D051379:Mice; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis / Q000503:physiopathology*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000502:physiology*
D017931:DNA Primers; D050796:STAT3 Transcription Factor