Open AccessPLZF Mediates the PTEN/AKT/FOXO3a Signaling in Suppression of Prostate Tumorigenesis
Author(s) -
Jianhua Cao,
Shu Zhu,
Wei Zhou,
Jie Li,
Chang Liu,
Hanqing Xuan,
Jie Yan,
Lin Zheng,
Lixin Zhou,
Jianxiu Yu,
Guoqiang Chen,
Yiran Huang,
Yu Zhang,
Feng Li
Publication year - 2013
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0077922
Subject(s) - pten , prostate cancer , cancer research , carcinogenesis , pi3k/akt/mtor pathway , protein kinase b , biology , signal transduction , cancer , microbiology and biotechnology , genetics
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.