PLZF mediates the PTEN/AKT/FOXO3a signaling in suppression of prostate tumorigenesis

PloS One
JingPing CaoLiXin Feng

Abstract

Promyelocytic leukemia zinc finger (PLZF) protein expression is closely related to the progression of human cancers, including prostate cancer (PCa). However, the according context of a signaling pathway for PLZF to suppress prostate tumorigenesis remains greatly unknown. Here we report that PLZF is a downstream mediator of the PTEN signaling pathway in PCa. We found that PLZF expression is closely correlated with PTEN expression in a cohort of prostate cancer specimens. Interestingly, both PTEN rescue and phosphoinositide 3-kinase (PI3K) inhibitor LY294002 treatment increase the PLZF expression in prostate cancer cell lines. Further, luciferase reporter assay and chromatin immunoprecipitation assay demonstrate that FOXO3a, a transcriptional factor phosphorylated by PI3K/AKT, could directly bind to the promoter of PLZF gene. These results indicate that PTEN regulates PLZF expression by AKT/FOXO3a. Moreover, our animal experiments also demonstrate that PLZF is capable of inhibiting prostate tumorigenesis in vivo. Taken together, our study defines a PTEN/PLZF pathway and would shed new lights for developing therapeutic strategy of prostate cancer.

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Citations

Dec 18, 2015·Stem Cells·Tong Ming LiuNg Shyh-Chang
May 23, 2015·Cell·Dan RobinsonArul M Chinnaiyan
Apr 5, 2016·Cell Biochemistry and Biophysics·Wenjing ZhuYu Peng
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Aug 10, 2021·DNA and Cell Biology·Hikmet KoseogluNur Buyru

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Methods Mentioned

BETA
PCR
immunoprecipitiation
ChIP
xenograft
immunoprecipitation
acetylation

Software Mentioned

SAS

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