Loss of p53 expression is accompanied by upregulation of beta-catenin in meningiomas: a concomitant reciprocal expression.
Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta-catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All the findings were analysed statistically. Our analysis showed that 47.5% of the 59 meningiomas demonstrated loss of expression of p53 protein. Moderate and strong p53 expression in the nuclei was observed in 8.5% and 6.8% of meningiomas respectively. Gross deletion of TP53 gene was observed in one meningioma, but nucleotide alterations were observed in 35.7% of meningiomas. In contrast, beta-catenin, the main Wnt signalling molecule, was upregulated in 71.2%, while strong expression was observed in 28.8% of meningiomas. The concomitant expressions of p53 and beta-catenin were investigated in the same patients. In the analysed meningiomas, the levels of the two proteins were significantly negatively correlated (P = 0.002). This indicates that meningiomas with lost p53 upregulate beta-catenin and activate Wnt signalling. Besides showing the reciprocal relationship between proteins, we also showed that the expression of p53 was significantly (P = 0.021) associated with higher meningioma grades (II and III), while beta-catenin upregulation was not associated with malignancy grades. Additionally, women exhibited significantly higher values of p53 loss when compared to males (P = 0.005). Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta-catenin in these tumours.
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia.|Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Nives
N
Pećina-Šlaus
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia.|Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia.
Anja
A
Kafka
Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.
Tomislav
T
Vladušić
Department of Pathology, School of Medicine, University of Zagreb, Zagreb, Croatia.|Hospital Centre 'Sisters of Charity', Zagreb, Croatia.
Davor
D
Tomas
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia.
Monika
M
Logara
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia.|University of Stuttgart Institute of Cell Biology and Immunology, D-70569 Stuttgart, Germany.
Josip
J
Skoko
Department of Biochemical Engineering, Faculty of Food Technology and Biotechnology, University of Zagreb, Zagreb, Croatia.
Reno
R
Hrašćan
D000328:Adult; D000368:Aged; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008297:Male; D008579:Meningioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods; D015398:Signal Transduction / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics*; D051176:beta Catenin / Q000096:biosynthesis* / Q000235:genetics
D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin
Wnt and p53 signalling; beta-catenin; meningioma; p53; protein expression