title: Identification of a Stat3-dependent transcription regulatory network involved in metastatic progression.
abstract: High levels of activated Stat3 are often found in human breast cancers and can correlate with poor patient outcome. We employed an activated ErbB2 mouse model of breast cancer to investigate the in vivo role of Stat3 in mammary tumor progression and found that Stat3 does not alter mammary tumor initiation but dramatically affects metastatic progression. Four-fold fewer animals exhibited lung metastases in the absence of Stat3 and a 12-fold reduction in the number of lung lesions was observed in animals bearing Stat3-null tumors when compared with the wild-type cohort. The decreased malignancy in Stat3-deficient tumors is attributed to a reduction in both angiogenic and inflammatory responses associated with a Stat3-dependent transcriptional cascade involving CCAAT/enhancer binding protein delta.
authors.affiliation: Goodman Cancer Centre, McGill University, Montreal, Quebec, Canada.
authors.forename: Jill J
authors.initials: JJ
authors.lastname: Ranger
authors.forename: David E
authors.initials: DE
authors.lastname: Levy
authors.forename: Solmaz
authors.initials: S
authors.lastname: Shahalizadeh
authors.forename: Michael
authors.initials: M
authors.lastname: Hallett
authors.forename: William J
authors.initials: WJ
authors.lastname: Muller
mesh_terms: D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D002471:Cell Transformation, Neoplastic; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000556:secondary; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic
chemical_list: D051743:CCAAT-Enhancer-Binding Protein-delta; D018719:Erb-b2 Receptor Tyrosine Kinases; D050796:STAT3 Transcription Factor; C494087:Stat3 protein, mouse; C524056:Erbb2 protein, mouse
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