Differential forms of p53 in medulloblastoma primary tumors, cell lines and xenografts

Philipova, Tzvetomira; Baryawno, Ninib; Hartmann, Wolfgang; Pietsch, Torsten; Druid, Henrik; Johnsen, John Inge; Ekström, Tomas J.

doi:10.3892/ijo.2010.884

Cited by 6 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For example, in leukaemia, a low molecular weight form of p53 is inversely correlated with the response to chemotherapy [39]. The presence of an even lower molecular weight p53 forms at 22 kDa has been reported in MB samples, including solid tissue tumours and MB xenografts [35]. We have previously reported that MEB-Med8A cells display a lower p53 band on western-blot [8] and here we show, using a combination of western blot and live cell imaging that the p53 activation is much slower and weaker in the MEB-Med8A cells compared to the p53 WT D283-MED cells (Fig.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Mir-34a Mimics Are Potential Therapeutic Agents for p53-Mutated and Chemo-Resistant Brain Tumour Cells

et al. 2014

View full text Add to dashboard Cite

Chemotherapeutic drug resistance and relapse remains a major challenge for paediatric (medulloblastoma) and adult (glioblastoma) brain tumour treatment. Medulloblastoma tumours and cell lines with mutations in the p53 signalling pathway have been shown to be specifically insensitive to DNA damaging agents. The aim of this study was to investigate the potential of triggering cell death in p53 mutated medulloblastoma cells by a direct activation of pro-death signalling downstream of p53 activation. Since non-coding microRNAs (miRNAs) have the ability to fine tune the expression of a variety of target genes, orchestrating multiple downstream effects, we hypothesised that triggering the expression of a p53 target miRNA could induce cell death in chemo-resistant cells. Treatment with etoposide, increased miR-34a levels in a p53-dependent fashion and the level of miR-34a transcription was correlated with the cell sensitivity to etoposide. miR-34a activity was validated by measuring the expression levels of one of its well described target: the NADH dependent sirtuin1 (SIRT1). Whilst drugs directly targeting SIRT1, were potent to trigger cell death at high concentrations only, introduction of synthetic miR-34a mimics was able to induce cell death in p53 mutated medulloblastoma and glioblastoma cell lines. Our results show that the need of a functional p53 signaling pathway can be bypassed by direct activation of miR-34a in brain tumour cells.

show abstract

Section: Discussionmentioning

confidence: 99%

“…The loss of TP53 due to the loss of chromosome 17p and isochromosome 17q are the most prevalent chromosomal abnormalities observed in MB [33]–[35]. Mutations in TP53 were found in 16% of MB and this is associated with a poor 5 year survival rate [36].…”

Section: Discussionmentioning

confidence: 99%

Mir-34a Mimics Are Potential Therapeutic Agents for p53-Mutated and Chemo-Resistant Brain Tumour Cells

et al. 2014

View full text Add to dashboard Cite

show abstract

“…A specific function for each isoform has yet to be defined, though some p53 isoforms have been shown to alter the function of the parent p53 (11–14, 17, 18). Δ40p53 (also known as ΔNp53, p44, or p53/47) was first identified in the mouse as a naturally occurring isoform present in Friend virus-induced tumors lacking full-length p53 [19,20]. Subsequent studies have focused on investigating endogenous p53 isoform expression in human cancers (11, 13, 14, 19).…”

Section: Introductionmentioning

confidence: 99%

“…Δ40p53 (also known as ΔNp53, p44, or p53/47) was first identified in the mouse as a naturally occurring isoform present in Friend virus-induced tumors lacking full-length p53 [19,20]. Subsequent studies have focused on investigating endogenous p53 isoform expression in human cancers (11, 13, 14, 19). The complexity of determining the frequency and mode of non-genomic p53 inactivation in cancers can be partly attributed to the function of the numerous p53 isoforms (1, 20).…”

Section: Introductionmentioning

confidence: 99%

p53 isoform profiling in glioblastoma and injured brain

et al. 2012

View full text Add to dashboard Cite

“…More than 12 p53 isoforms have been reported to date, namely, p53α (the canonical wild-type p53), p53β, p53γ, Δ40p53α, Δ40p53β, Δ40p53γ, Δ133p53α, Δ133p53β, Δ133p53γ, Δ160p53α, Δ160p53β, and Δ160p53γ. The p53 isoform expression pattern is remarkably altered in breast cancer[20], kidney cancer[21,22], colorectal cancer[23], ovarian malignancy[24-27], leukemia[28], medulloblastoma[29], and neuroblastoma[30]. Accumulating evidence has indicated that some of these isoforms function as p53 co-activators ( e.g ., p53β), while others function as its antagonists with oncogenic characteristics ( e.g ., Δ40p53α and Δ133p53α)[31-33].…”

Section: Discussionmentioning

confidence: 99%

Role of Δ133p53 isoform in NF-κB inhibitor PDTC-mediated growth inhibition of MKN45 gastric cancer cells

Zhang¹,

Sang²,

Wang³

et al. 2017

WJG

View full text Add to dashboard Cite

AIMTo investigate the role of Δ133p53 isoform in nuclear factor-κB (NF-κB) inhibitor pyrrolidine dithiocarbamate (PDTC)-mediated growth inhibition of MKN45 gastric cancer cells.METHODSThe growth rate of MKN45 cells after treatment with different concentrations of only PDTC or PTDC in combination with cisplatin was detected by the CCK-8 assay. mRNA expression levels of Δ133p53, p53β, and the NF-κB p65 subunit and p65 protein levels were detected by reverse transcription-polymerase chain reaction (RT-PCR) and immunofluorescence, respectively. Growth of MKN45 cells was significantly inhibited by PDTC alone in a dose-dependent manner (P < 0.01). Moreover, the inhibitory effect of cisplatin was remarkably enhanced in a dose-dependent manner by co-treatment with PDTC (P < 0.01).RESULTSRT-PCR analysis revealed that mRNA expression of p65 was curbed significantly in a dose-dependent manner by treatment with only PDTC (P < 0.01), and this suppressive effect was further enhanced when co-treated with cisplatin (P < 0.01). With respect to the other p53 isoforms, mRNA level of Δ133p53 was significantly reduced in a dose-dependent manner by treatment with only PDTC or PTDC in combination with cisplatin (P < 0.01), whereas p53β mRNA expression was not altered by PDTC treatment (P > 0.05). A similar tendency of change in p65 protein expression, as observed for the corresponding mRNA, was detected by immunofluorescence analysis (P < 0.01). Pearson correlation analysis demonstrated that Δ133p53 and p65 mRNA expression levels were positively related, while no significant relationship was observed between those of p65 and p53β (r = 0.076, P > 0.01).CONCLUSIONΔ133p53 isoform (not p53β) is required in PDTC-induced inhibition of MKN45 gastric cancer cells, indicating that disturbance in the cross-talk between p53 and NF-κB pathways is a promising target in pharmaceutical research for the development of treatment strategies for gastric cancer.

show abstract

Differential forms of p53 in medulloblastoma primary tumors, cell lines and xenografts

Cited by 6 publications

References 27 publications

Mir-34a Mimics Are Potential Therapeutic Agents for p53-Mutated and Chemo-Resistant Brain Tumour Cells

Mir-34a Mimics Are Potential Therapeutic Agents for p53-Mutated and Chemo-Resistant Brain Tumour Cells

p53 isoform profiling in glioblastoma and injured brain

Role of Δ133p53 isoform in NF-κB inhibitor PDTC-mediated growth inhibition of MKN45 gastric cancer cells

Contact Info

Product

Resources

About