title: Silencing of CD24 Enhances the PRIMA-1-Induced Restoration of Mutant p53 in Prostate Cancer Cells.
abstract: In prostate cancer cells, there is CD24-dependent inactivation of mutant p53, but the mechanism and its significance remain largely unknown. Here, we validated this observation and explored the therapeutic potential of targeting CD24 in TP53 mutant prostate cancer cells.
  
  
  
  Overall, 553 prostate cancers (522 formalin-fixed paraffin-embedded and 31 frozen tissues) were assessed for protein or mRNA expression of CD24 and TP53 The effects of CD24 on p53-dependent transcriptional regulation, cancer cell growth, the cell cycle, apoptosis, and mutant p53 restoration were also determined.
  
  
  
  As determined with three sample cohorts, CD24 and p53 were not expressed in prostate epithelial cells but in prostate cancer cells in 48% of cases for CD24 and 16% of cases for p53 (mutant form). Expressions of CD24 and mutant p53 were more frequently observed in late-stage and metastatic prostate tumors. Mutant p53 accompanied with CD24 was expressed in most cases (91.6%, 76/83). Silencing of CD24 increased the transcriptional activity of p53 target genes, such as CDKNA1, VDR, and TP53INP1, leading to suppression of p53-dependent cell growth, cell-cycle arrest, and apoptosis in most TP53-mutant prostate cancer cells. Silencing of CD24 enhanced restoration of PRIMA-1-induced mutant p53 in endogenous TP53(P223L/V274F) DU145 cells and in PC3 cells transfected with TP53(R273H) CONCLUSIONS: In human prostate cancers, there is CD24-dependent inactivation of mutant p53. The coexpression of CD24 and p53 may help identify aggressive cancers. Targeting CD24 provides a strategy to enhance mutant p53-restoring therapies, especially in patients with TP53(R273H) prostate cancer. Clin Cancer Res; 22(10); 2545-54. ©2015 AACR.
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama. Institute for the Endemic Fluorosis Control, Chinese Center for Endemic Disease Control, Harbin Medical University, Harbin, P.R. China.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama. Department of Pediatric Surgery, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Bin
authors.initials: B
authors.lastname: Yi
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama. Department of Integrative Endemic Area, Tongji Hospital of Huazhong University of Science and Technology, Wuhan, P.R. China.
authors.forename: Chao
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Dongquan
authors.initials: D
authors.lastname: Chen
authors.affiliation: Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, Alabama. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Sejong
authors.initials: S
authors.lastname: Bae
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Shi
authors.initials: S
authors.lastname: Wei
authors.affiliation: Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Rong-Jun
authors.initials: RJ
authors.lastname: Guo
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Changming
authors.initials: C
authors.lastname: Lu
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama.
authors.forename: Lisa L H
authors.initials: LL
authors.lastname: Nguyen
authors.affiliation: Department of Biomedical Sciences, Mercer University, Savannah, Georgia.
authors.forename: Wei-Hsiung
authors.initials: WH
authors.lastname: Yang
authors.affiliation: Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, Atlanta, Georgia.
authors.forename: James W
authors.initials: JW
authors.lastname: Lillard
authors.affiliation: Provincial Key Laboratory on Molecular and Chemical Genetic, The Second Hospital of Jilin University, Changchun, P.R. China. runhua@uab.edu lwang12@uab.edu xingyizhang@live.com.
authors.forename: Xingyi
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama. runhua@uab.edu lwang12@uab.edu xingyizhang@live.com.
authors.forename: Lizhong
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Genetics, University of Alabama at Birmingham, Birmingham, Alabama. Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, Alabama. runhua@uab.edu lwang12@uab.edu xingyizhang@live.com.
authors.forename: Runhua
authors.initials: R
authors.lastname: Liu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000235:genetics; D051927:CD24 Antigen / Q000235:genetics*; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D055815:Young Adult
chemical_list: D051927:CD24 Antigen; C497889:CD24 protein, human; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C446290:PRIMA1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53