title: Transforming growth factor-β 1 enhances the invasiveness of breast cancer             cells by inducing a Smad2-dependent epithelial-to-mesenchymal transition.
abstract: Metastasis is unequivocally the most lethal aspect of breast cancer and             the most prominent feature associated with disease recurrence, the molecular mechanisms             whereby epithelial-to-mesenchymal transition (EMT) mediates the initiation and             resolution of breast cancer metastasis remains poorly understood. Transforming             growth factor-β1 (TGF-β1) is a multifunctional cytokine that is intimately involved             in regulating numerous physiological processes, including cellular differentiation,             homeostasis and EMT. Recent findings have implicated high levels of TGF-β1 were             associated with poor outcome, whereas inhibition of TGF-β signaling reduces metastasis             in breast cancer, suggesting that the chemo-therapeutic targeting of TGF-β1 or             TGF-β signaling may offer new inroads in ameliorating metastatic disease in breast             cancer patients. In this study, we showed immunohistochemical evidence for EMT,             which is associated with TGF-β1 expression, at the invasion front of breast cancer             in vivo. The data also indicated that human breast cancer cell lines, MCF-7 and             MDA-MB-435S, of epithelial cell characteristics were induced to undergo EMT by             TGF-β1 and dependent on the Smad2 signaling pathway. Following TGF-β1 treatment,             cells showed dramatic morphological changes assessed by phase contrast microscopy,             accompanied by decreased epithelial marker and increased mesenchymal markers.             Importantly, cell invasion was also enhanced in the EMT process, while knockdown             of the Smad2 gene by silencing siRNA partially inhibited these effects in MDA-MB435S             (P<0.05). These data suggested that EMT of breast cancer induced by TGF-β1             is dependent on Smad2 signaling and promotes breast cancer cell metastasis.
authors.affiliation: Department of Breast Surgery, The Affiliated Hospital of Qingdao University Medical College, Qingdao 266003, PR China.
authors.forename: Zhi-Dong
authors.initials: ZD
authors.lastname: Lv
authors.forename: Bin
authors.initials: B
authors.lastname: Kong
authors.forename: Jian-Guo
authors.initials: JG
authors.lastname: Li
authors.forename: Hui-Li
authors.initials: HL
authors.lastname: Qu
authors.forename: Xin-Gang
authors.initials: XG
authors.lastname: Wang
authors.forename: Wei-Hong
authors.initials: WH
authors.lastname: Cao
authors.forename: Xiao-Yi
authors.initials: XY
authors.lastname: Liu
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Zhao-Chuan
authors.initials: ZC
authors.lastname: Yang
authors.forename: Hui-Mian
authors.initials: HM
authors.lastname: Xu
authors.forename: Hai-Bo
authors.initials: HB
authors.lastname: Wang
mesh_terms: D017209:Apoptosis; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002448:Cell Adhesion; D002465:Cell Movement; D049109:Cell Proliferation; D058750:Epithelial-Mesenchymal Transition; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D009361:Neoplasm Invasiveness; D010766:Phosphorylation; D034741:RNA, Small Interfering / Q000235:genetics; D051899:Smad2 Protein / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D046888:Tissue Array Analysis; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D034741:RNA, Small Interfering; C497782:SMAD2 protein, human; D051899:Smad2 Protein; D053773:Transforming Growth Factor beta1