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Supplementary Figures 1-4 and Tables 1-4 from Silencing of CD24 Enhances the PRIMA-1–Induced Restoration of Mutant p53 in Prostate Cancer Cells

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posted on 2023-03-31, 18:45 authored by Wei Zhang, Bin Yi, Chao Wang, Dongquan Chen, Sejong Bae, Shi Wei, Rong-Jun Guo, Changming Lu, Lisa L.H. Nguyen, Wei-Hsiung Yang, James W. Lillard, Xingyi Zhang, Lizhong Wang, Runhua Liu

Figure S1: (Overexpression of CD24 mRNA in human PCa tissue based on analysis of three datasets); Figure S2: (Nuclear CD24 and p53 staining in human PCa cases); Figure S3: (The sequence-specific DNA binding sites of p53 in its target genes); Figure S4: (CD24-dependent inactivation of mutant p53 and cell cycle arrast in human LNCaP cells).

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NIH

NCI

Department of Defense

UAB

Mercer University Seed

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ARTICLE ABSTRACT

Purpose: 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.Experimental Design: 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.Results: 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 TP53P223L/V274F DU145 cells and in PC3 cells transfected with TP53R273H.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 TP53R273H prostate cancer. Clin Cancer Res; 22(10); 2545–54. ©2015 AACR.