engleski

Wnt signalling in human brain tumors

Gene instabilities of key players of wnt signaling, adenomatous polyposis coli (APC), axin (AXIN-1) and E-cadherin (CDH1) were tested by PCR/loss of heterozygosity (LOH). Beta-catenin (CTNNB1) was investigated by heteroduplex method. Proteins were investigated by immunohistochemistry and Image analysis. Changes of CDH1 gene were found almost exclusively in meningiomas with correlation at 0.002 level. Our analysis showed LOHs of CDH1 gene in 31% of meningiomas examined. Changes of APC gene were more frequent and distributed among different tumor types, with glioblastomas showing the highest percentage. Observed LOHs of APC were distributed to: 60% of glioblastomas, 47% of meningiomas, 20% of astocytomas, and 17% neurinomas. Immunostaining showed that meningioma samples with LOHs were accompanied with the absence of APC protein or presence of mutant APC proteins (P=0.001). We also showed that nuclear localization of beta-catenin correlates to APC genetic changes (P=0.0001). The investigation on beta-catenin demonstrated 10% of heteroduplexes in β -catenin’ s exon 3. We found LOH of AXIN-1 in 6.3% of glioblastomas, 1 LOH in neuroepithelial dysembrioplastic tumor and 1 in medulloblastoma. Comparison of mean values of relative increase of axin and beta-catenin shows that they are reversely proportional (P=0.014). Moreover, relative quantity of beta-catenin protein in patients with AXIN-1 LOH was higher in comparison to patients without LOH (P=0.040).

wnt signalling; brain tumors; loss of heterozygosity

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