Exogenously introduced wild-type and mutant p53 have recently been reported to enhance the human epidermal growth factor receptor (EGF-R) gene promoter activity in p53-deficient Saos2 osteosarcoma cells.
Three genes, CD137L, CDC42 binding protein kinase gamma and Follistatin, were identified as novel direct p53 target genes that exhibited growth-suppressive effects on osteosarcoma cell lines.
We compared ceramide levels before and after DNA damage in human osteosarcoma (U2OS) and colon cancer (HCT116) cells that were either expressing or deficient in p53.
Screening of 288 OS and 1,090 tumors of other types revealed evidence for TP53 rearrangements in 46 (16%) OS, while none were detected in other tumor types, indicating this rearrangement to be highly specific to OS.
The study provides evidence supporting the association of MDM2 SNP309 with high-grade osteosarcoma risk in females and shows that TP53Arg72Pro has a prognostic value for overall survival and EFS in osteosarcoma patients.
Microarray and p53 chromatin immunoprecipitation combined with sequencing (ChIP-seq) datasets of the OS cell line U2OS treated with distinct drugs were acquired from the Gene Expression Omnibus and differentially-expressed genes (DEGs) were screened for alignment analysis.
The event-free survival (EFS) was worse in Ewing sarcoma patients with p16INK4 and p14ARF mutation/deletion than in those without the mutation/deletion (P = 0.019), and EFS was worse in osteosarcoma patients with TP53 alterations than in those without TP53 alterations (P = 0.048).
The atypical subgroup showed similar results to those of the osteosarcoma group (P < 0.001). p53 protein was detected in 4 (13%) osteoblastomas (3 of these were atypical osteoblastoma), and 4 osteosarcomas (23%) also showed p53 positivity.
This study warrants a future evaluation of this formulation for gene silencing efficiency of mutant p53 in tissue culture and animal models for the treatment of osteosarcoma.
Whereas, overexpression of microRNA‑152 targets DKK1 to inhibit cell proliferation, induce apoptosis, and promote LDH activity, caspase-3/9 activities and Bax/Bcl-2 and p53 protein expression levels of osteosarcoma through inactivation of the Wnt/β-catenin signaling pathway.
The involvement of p53 in tumour response was investigated in an osteosarcoma cell line, SAOS, which is null for p53 and is highly sensitive to BBR 3464, and in the same cells following introduction of the wild-type p53 gene.
To address this issue in osteosarcomas, we examined the status of E2F1 relative to cell proliferation and apoptosis in a clinical setting of human primary osteosarcomas and in E2F1-inducible osteosarcoma cell line models that are wild-type and deficient for p53.
In our studies of the pediatric solid tumors neuroblastoma and osteosarcoma, we find overexpression of ΔNp63; however, there is no correlation of ΔNp63 expression with p53 mutation status.