1847-1857) develop a new mouse model of osteosarcoma in which a GOF mutant p53 allele is expressed specifically in osteoblasts, while the tumor microenvironment remains wild type for p53, allowing for the study of cell-autonomous functions.
Osteosarcoma development is dependent on loss of p53 and potentiated by loss of pRb, revealing a dominance of p53 mutation in the development of osteosarcoma.
Osteosarcoma is associated with massive genomic instability, making it problematic to identify driver genes using human tumors or prototypical mouse models, many of which involve loss of Trp53 function.
Tumor protein p53 (TP53), mitogen-activated protein kinase 1 (MAPK1) and estrogen receptor 1 (ESR1) were identified the most important osteosarcoma‑associated genes, with the highest levels of topological properties.
A polysaccharide from Enterobacter cloacae induces apoptosis of human osteosarcoma cells through the activation of p53 and mitochondrial intrinsic pathway.
Aberrant expression of the transcription factor, runt-related transcription factor 2 (RUNX2), is a key pathological feature in osteosarcoma and associated with loss of p53 and miR-34 expression.
According to our findings AgNPs are able to kill osteosarcoma cells independently from their actual p53 status and induce p53-independent cancer cell apoptosis.
After SOX4 gene silencing, the protein expression levels of Bax, Caspase-3, and P53 in osteosarcoma cells were significantly elevated, while the protein expression levels of Bcl-2, MMP2, and MMP9 were obviously decreased.
All those cases of osteoblastic OS and MFH of bone that had p53 mutations, with the exception of one case of MFH of bone that had a silent mutation, showed aggressive biologic behavior (dead of disease within 12 mo), in contrast to the MFH-like OS cases (alive without disease at 22 mo).
Alterations of the p53/MDM2 pathway are frequent in OS and usually represent mutually exclusive tumorigenic events. p53 does not appear to be a major determinant of proliferative rate in OS.
Although many genes, such as p53 and Rb1, have been shown to be mutated, deregulation of the canonical Wnt/β-catenin signaling pathway is frequently observed in OS.
Although mutations in TP53 were thought to be relatively low in sarcomas, modern techniques including whole-genome sequencing have recently illuminated unappreciated alterations in TP53 in osteosarcoma.
Anti-cancer drug adriamycin (ADR) treatment induced cell death in <i>p53</i>-wild-type human osteosarcoma U2OS cells, and this was accompanied by a remarkable accumulation of p53 and γH2AX.
As a result, methyl 2,5-dihydromethylcinnimate (2,5-MeC), a tyrosine kinase inhibitor, enhanced expression and/or stability of PML proteins and induced PML-NB formation in p53 null H1299 cells established from non-small cell lung cancer (NSCLC) and wild-type p53-expressing U2OS cells derived from osteosarcoma.
As the genes of p53 and/or retinoblastoma (Rb) are mutated in the major part of osteosarcomas (OS), we aimed to study the effect of p53 and Rb transgenes on a panel of five different osteosarcoma cell lines.
Ascochlorin, a prenylphenol antitumor antibiotic, profoundly increases the expression of endogenous p53 by increasing protein stability in the human osteosarcoma cells and human colon cancer cells.
At advanced ages, p53 mKO mice began to die prematurely and had an increased incidence of osteosarcoma, precluding analyses of muscle mass and function in very old p53 mKO mice.
Based on recommendation of the Cochrane Collaboration, this meta-analysis was conducted using data from the 17 published studies to evaluate the association of p53 alterations with clinical outcome of osteosarcoma patients.
By utilizing the clinical information in GSE21257, 10 critical genes associated with osteosarcoma prognosis were obtained, including CTP synthase 2 (CTPS2), tumor protein p53 inducible protein 3 (TP53I3) and solute carrier family 1 member 1 (SLC1A1).
Characterization of two tumor suppressor genes, p53 and RB1, that have been implicated in osteosarcoma formation indicated that p53 was altered in five of six osteosarcoma cell lines, whereas RB1 was altered in only two or six of these cell lines.