PUBLICATION

PTEN Insufficiency Increases Breast Cancer Cell Metastasis In Vitro and In Vivo in a Xenograft Zebrafish Model

Authors
Chiang, K.C., Hsu, S.Y., Lin, S.J., Yeh, C.N., Pang, J.H., Wang, S.Y., Hsu, J.T., Yeh, T.S., Chen, L.W., Kuo, S.F., Cheng, Y.C., Juang, H.H.
ID
ZDB-PUB-160729-4
Date
2016
Source
Anticancer research   36: 3997-4005 (Journal)
Registered Authors
Lin, Sheng-Jia
Keywords
EMT, PTEN, breast cancer, metastasis, zebrafish
MeSH Terms
  • Animals
  • Breast Neoplasms/genetics*
  • Breast Neoplasms/pathology
  • CCN Intercellular Signaling Proteins/biosynthesis
  • Cell Movement/genetics
  • Disease Models, Animal
  • Epithelial-Mesenchymal Transition/genetics*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Gene Knockdown Techniques
  • Homeodomain Proteins/biosynthesis
  • Humans
  • MCF-7 Cells
  • Matrix Metalloproteinase 2/biosynthesis
  • Matrix Metalloproteinase 9/biosynthesis
  • Neoplasm Invasiveness/genetics*
  • Neoplasm Metastasis
  • PTEN Phosphohydrolase/biosynthesis
  • PTEN Phosphohydrolase/genetics*
  • Repressor Proteins/biosynthesis
  • Snail Family Transcription Factors/biosynthesis
  • Twist-Related Protein 1/biosynthesis
  • Wnt1 Protein/biosynthesis
  • Xenograft Model Antitumor Assays
  • Zebrafish
  • Zebrafish Proteins/biosynthesis
  • Zinc Finger E-box-Binding Homeobox 1/biosynthesis
PubMed
27466505
Abstract
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.
Migration and invasion assay, western blot, immunofluorescent staining and zebrafish animal model were applied.
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.
Our findings reveal new therapeutic targets for breast cancer patients with PTEN insufficiency.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping