title: PTEN Insufficiency Increases Breast Cancer Cell Metastasis In Vitro and In Vivo in a Xenograft Zebrafish Model.
abstract: OBJECTIVE
  Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) insufficiency is commonly found in breast cancer patients with metastasis. We investigated the mechanisms by which PTEN affects breast cancer metastatic behavior.
  
  
  METHODS
  Migration and invasion assay, western blot, immunofluorescent staining and zebrafish animal model were applied.
  
  
  RESULTS
  We showed that PTEN insufficiency induced an increase in MCF-7 cell migration and invasion through induction of epithelial-mesenchymal transition (EMT), which was triggered by up-regulation of the EMT-inducing transcriptional factors Zeb1, Zeb2, Snail, Slug and Twist. Simultaneously, E-cadherin expression was inhibited and P-cadherin was up-regulated. Further, WNT1 inducible signaling pathway protein 1 (WISP1) and lipocalin-2 (LCN2) expressions were increased after PTEN knockdown in MCF-7 cells, which also exhibited increased filamentous actin (F-actin) synthesis and extracellular matrix metalloproteinase-2 (MMP-2) and MMP-9 expression. We further showed that PTEN knockdown in MCF-7 cells could increase cell migration in the xenograft zebrafish model.
  
  
  CONCLUSIONS
  Our findings reveal new therapeutic targets for breast cancer patients with PTEN insufficiency.
authors.affiliation: General Surgery Department, Chang Gung University, Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C. Zebrafish Center of Keelung Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C.
authors.forename: Kun-Chun
authors.initials: KC
authors.lastname: Chiang
authors.affiliation: Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.
authors.forename: Shu-Yuan
authors.initials: SY
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, R.O.C.
authors.forename: Sheng-Jia
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Department of General Surgery, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Yeh
authors.affiliation: Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C.
authors.forename: Jong-Hwei S
authors.initials: JH
authors.lastname: Pang
authors.affiliation: Department of General Surgery, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
authors.forename: Shang-Yu
authors.initials: SY
authors.lastname: Wang
authors.affiliation: Department of General Surgery, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
authors.forename: Jun-Te
authors.initials: JT
authors.lastname: Hsu
authors.affiliation: Department of General Surgery, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C.
authors.forename: Ta-Sen
authors.initials: TS
authors.lastname: Yeh
authors.affiliation: Department of Gastroenterology, Chang Gung University, Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C.
authors.forename: Li-Wei
authors.initials: LW
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Chang Gung University, Chang Gung Memorial Hospital, Keelung, Taiwan, R.O.C.
authors.forename: Sheng-Fong
authors.initials: SF
authors.lastname: Kuo
authors.affiliation: Graduate Institute of Biomedical Sciences, College of Medicine, Chang-Gung University, Taoyuan, Taiwan, R.O.C. yccheng@mail.cgu.edu.tw hhj143@mail.cgu.edu.tw.
authors.forename: Yi-Chuan
authors.initials: YC
authors.lastname: Cheng
authors.affiliation: Department of Anatomy, College of Medicine, Chang Gung University, Taoyuan, Taiwan, R.O.C. Department of Urology, Chang Gung University, Chang Gung Memorial Hospital, Taoyuan, Taiwan, R.O.C. yccheng@mail.cgu.edu.tw hhj143@mail.cgu.edu.tw.
authors.forename: Horng-Heng
authors.initials: HH
authors.lastname: Juang
mesh_terms: D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D055511:CCN Intercellular Signaling Proteins / Q000096:biosynthesis; D002465:Cell Movement / Q000235:genetics; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D018398:Homeodomain Proteins / Q000096:biosynthesis; D006801:Humans; D061986:MCF-7 Cells; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics*; D009362:Neoplasm Metastasis; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis / Q000235:genetics*; D012097:Repressor Proteins / Q000096:biosynthesis; D000071250:Snail Family Transcription Factors / Q000096:biosynthesis; D051879:Twist-Related Protein 1 / Q000096:biosynthesis; D051155:Wnt1 Protein / Q000096:biosynthesis; D023041:Xenograft Model Antitumor Assays; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000096:biosynthesis; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1 / Q000096:biosynthesis
chemical_list: D055511:CCN Intercellular Signaling Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins; D000071250:Snail Family Transcription Factors; D051879:Twist-Related Protein 1; D051155:Wnt1 Protein; C492363:ZEB2 protein, human; D029961:Zebrafish Proteins; D000074165:Zinc Finger E-box Binding Homeobox 2; D000071799:Zinc Finger E-box-Binding Homeobox 1; C552351:ccn4a protein, zebrafish; C096850:snai1b protein, zebrafish; C583292:zeb1b protein, zebrafish; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9
keywords: EMT; PTEN; breast cancer; metastasis; zebrafish