engleski

Molecular components of the wnt signaling are changed in meningioma

The malfunctioning of wnt signal transduction pathway is responsible for tumorigenesis in many different tissues. Our group was studying molecular components of wnt signaling, namely, APC, beta-catenin and E-cadherin in meningiomas, since the molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. The main signaling molecule of the pathway is β-catenin, but APC is a critical component of its destruction machinery, while E-cadherin is indirect modulator of the pathway connected also to the adherens junctions. Gene changes were tested by polymerase chain reaction/loss of heterozygosity (LOH) using Restriction Fragment Length Polymorphism (RFLP) method and MSI analysis. Protein expression was analyzed by immunohistochemistry. The analysis regarding APC gene demonstrated LOH in 47% of investigated patients. Immunostaining showed that samples with LOHs were accompanied with the absence of APC protein expression or presence of mutant APC proteins (2 =13.81, df = 2, P0.001). We also showed that nuclear localization of beta-catenin correlates to APC genetic changes (2 =21, 96, df = 2, P0.0001). When investigating E-cadherin’s changes in meningiomas, 32% of investigated samples harbored LOH of this tumor suppressor gene. Moreover MSI was detected in 11% of meningioma cases. Immunostaining showed that overall 73% of samples had downregulation of E-cadherin expression. Intense downregulation of E-cadherin was noticed in tumors with grades II and III. We also noticed that 36.4% of samples with lower E-cadherin expression had beta-catenin located in the nucleus. Also, 75% of samples with genetic changes had beta-catenin in the nucleus. Our findings demonstrated that there is significant association between the genetic changes of CDH1 and the nuclear localization of beta-catenin protein (2 =5.25, df =1. P0.022). Beta-catenin was progressively upregulated from meningothelial to atypical, while 60% of anaplastic showed upregulation and nuclear localization of the protein. Our investigation indicates that changes of wnt signaling molecular components play a role in meningioma formation.

wnt signaling; meningioma

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