PDZ-containing 1 acts as a suppressor of pancreatic cancer by regulating PTEN phosphorylation

Oncotarget
Qiang MaTonghua Liu

Abstract

Phosphorylation is a recently established cause of phosphatase and tensin homolog (PTEN) gene inactivation, which leads to defect tumour-suppressor function. In pancreatic cancer, this phenomenon has not been reported. Based on database and clinical sample analyses, we found that PTEN phosphorylation occurs in pancreatic ductal adenocarcinoma patient tissues and cell lines, and we aimed to find a method for dephosphorylation. PDZ-containing 1 (PDZK1), a tumour-associated protein that shares its PDZ-binding sequence with the carboxyl-terminal domain of PTEN, was significantly down-regulated in pancreatic cancer as compared to adjacent non-tumour tissues. In vitro, PDZK1 overexpression reversed the proliferation and migration abilities of pancreatic cancer cells and led to significantly decreased PTEN phosphorylation and AKT phosphorylation by interacting with wild-type PTEN. In addition, a transcription factor-activation assay supported that PDZK1 overexpression enhanced the anti-oncogene function of PTEN by regulating the activities of its downstream transcription factors, including p53, NF-κB, and FOXO1. In vivo, nude mice stably over-expressing PDZK1 had lower tumour weights and volumes and showed significantly down-regulated...Continue Reading

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Methods Mentioned

BETA
transfection
xenograft
electrophoresis
PCR
fluorescence microscopy
surgical resection

Software Mentioned

Bio
Life DP
SPSS
ImagePro Plus
GraphPad Prism
Bio Life DP
Image J
Gene Set Enrichment Analysis ( GSEA )
GraphPad
GSEA

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