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

BACKGROUND/AIM: 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.

MATERIALS AND 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.

CONCLUSION: Our findings reveal new therapeutic targets for breast cancer patients with PTEN insufficiency.