title: PLZF mediates the PTEN/AKT/FOXO3a signaling in suppression of prostate tumorigenesis.
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.
authors: Institute of Health Sciences, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences & Shanghai Jiao Tong University School of Medicine, Shanghai, China ; Laboratory for Germ Cell Research, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine (SJTU-SM), Shanghai, China ; Department of Pathophysiology, Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of Education, SJTU-SM, Shanghai, China.
authors: JingPing
authors: J
authors: Cao
authors: Shu
authors: S
authors: Zhu
authors: Wei
authors: W
authors: Zhou
authors: Jie
authors: J
authors: Li
authors: Chang
authors: C
authors: Liu
authors: HanQing
authors: H
authors: Xuan
authors: Jie
authors: J
authors: Yan
authors: Lin
authors: L
authors: Zheng
authors: LiXin
authors: L
authors: Zhou
authors: JianXiu
authors: J
authors: Yu
authors: GuoQiang
authors: G
authors: Chen
authors: YiRan
authors: Y
authors: Huang
authors: Zhuo
authors: Z
authors: Yu
authors: LiXin
authors: L
authors: Feng
mesh_terms: D000818:Animals; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008819:Mice, Nude; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D011401:Promoter Regions, Genetic / Q000235:genetics; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D011471:Prostatic Neoplasms / Q000473:pathology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C499517:FOXO3 protein, human; D000071316:Forkhead Box Protein O3; D051858:Forkhead Transcription Factors; D051741:Kruppel-Like Transcription Factors; D000075722:Promyelocytic Leukemia Zinc Finger Protein; D025521:Tumor Suppressor Proteins; C092037:ZBTB16 protein, human; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human