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

来源：

MOLECULAR CARCINOGENESIS | 2010年 / 49卷 / 02期

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

页码：114 / 120

页数：7

共 36 条

[21] Signal transduction in transgenic mouse models of human breast cancer - Implications for human breast cancer [J].

Marcotte, Richard ;

Muller, William J. .

JOURNAL OF MAMMARY GLAND BIOLOGY AND NEOPLASIA, 2008, 13 (03) :323-335

[22] Biology, prognosis and response to therapy of breast carcinomas according to HER2 score [J].

Menard, S. ;

Balsari, A. ;

Tagliabue, E. ;

Camerini, T. ;

Casalini, P. ;

Bufalino, R. ;

Castiglioni, F. ;

Carcangiu, M. L. ;

Gloghini, A. ;

Scalone, S. ;

Querzoli, P. ;

Lunardi, M. ;

Molino, A. ;

Mandara, M. ;

Mottolese, M. ;

Marandino, F. ;

Venturini, M. ;

Bighin, C. ;

Cancello, G. ;

Montagna, E. ;

Perrone, F. ;

De Matteis, A. ;

Sapino, A. ;

Donadio, M. ;

Battelli, N. ;

Santinelli, A. ;

Pavesi, L. ;

Lanza, A. ;

Zito, F. A. ;

Labriola, A. ;

Aiello, R. A. ;

Caruso, M. ;

Zanconati, F. ;

Mustacchi, G. ;

Barbareschi, M. ;

Frisinghelli, M. ;

Russo, R. ;

Carrillo, G. .

ANNALS OF ONCOLOGY, 2008, 19 (10) :1706-1712

[23] SINGLE-STEP INDUCTION OF MAMMARY ADENOCARCINOMA IN TRANSGENIC MICE BEARING THE ACTIVATED C-NEU ONCOGENE [J].

MULLER, WJ ;

SINN, E ;

PATTENGALE, PK ;

WALLACE, R ;

LEDER, P .

CELL, 1988, 54 (01) :105-115

[24]

Nanni P, 2000, INT J CANCER, V87, P186, DOI 10.1002/1097-0215(20000715)87:2<186::AID-IJC5>3.0.CO

[25]

2-1

[26] 15-Deoxy-Δ12,14-prostaglandin J2 induces apoptosis in human malignant B cells:: an effect associated with inhibition of NF-κB activity and down-regulation of antiapoptotic proteins [J].

Piva, R ;

Gianferretti, P ;

Ciucci, A ;

Taulli, R ;

Belardo, G ;

Santoro, MG .

BLOOD, 2005, 105 (04) :1750-1758

[27] Functional validation of the analplastic lymphoma kinase signature identifies CEBPB and BCL2A1 as critical target genes [J].

Piva, Roberto ;

Pellegrino, Elisa ;

Mattioli, Michela ;

Agnelli, Luca ;

Lombardi, Luigia ;

Boccalatte, Francesco ;

Costa, Giulia ;

Ruggeri, Bruce A. ;

Cheng, Mangeng ;

Chiarle, Roberto ;

Palestro, Giorgio ;

Neri, Antonino ;

Inghirami, Giorgio .

JOURNAL OF CLINICAL INVESTIGATION, 2006, 116 (12) :3171-3182

[28] Activation of Stat3 by Heregulin/ErbB-2 through the Co-Option of Progesterone Receptor Signaling Drives Breast Cancer Growth [J].

Proietti, Cecilia J. ;

Rosemblit, Cinthia ;

Beguelin, Wendy ;

Rivas, Martin A. ;

Diaz Flaque, Maria Celeste ;

Charreau, Eduardo H. ;

Schillaci, Roxana ;

Elizalde, Patricia V. .

MOLECULAR AND CELLULAR BIOLOGY, 2009, 29 (05) :1249-1265

[29] Identification of a Stat3-Dependent Transcription Regulatory Network Involved in Metastatic Progression [J].

Ranger, Jill J. ;

Levy, David E. ;

Shahalizadeh, Solmaz ;

Hallett, Michael ;

Muller, William J. .

CANCER RESEARCH, 2009, 69 (17) :6823-6830

[30] ErbB-2 activates Stat3α in a Src- and JAK2-dependent manner [J].

Ren, ZY ;

Schaefer, TS .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (41) :38486-38493

← 1 2 3 4 →