engleski

Involvement of key components of Wnt signaling in human astrocytic brain tumors

Molecular landscape of human brain tumors is still inadequately explained. In the present study key players of wnt signaling, adenomatous polyposis coli (APC), axin (AXIN1) E-cadherin (CDH1) and beta-catenin (CTNNB1) were investigated in the set of human astrocytic brain tumors. Genetic changes were tested by PCR/loss of heterozygosity (LOH). Beta-catenin (CTNNB1) was investigated by heteroduplex method. Relevant proteins were investigated by immunohistochemistry. Changes of APC gene were frequent and distributed among different tumor grades, with glioblastomas showing the highest percentage (60%). LOHs were also detected in 20% of diffuse astocytomas (II). AXIN1 was tested with D16S521 microsatellite marker and LOH was found in 10% of glioblastomas (IV) while astrocytomas of grades I, II and III did not demonstrate LOH. The investigation on beta-catenin demonstrated 8.3% of samples with potential mutations. Changes of CDH1 gene were not detected in our study. In 31% of glioblastomas and 22% of astrocytomas downregulation of axin proteins was detected. The majority of glioblastomas (69%) had axin localized in the cytoplasm, while in 31% it was observed in the nucleus. Astrocytomas also demonstrated nuclear localization in 44% of cases. In 50% of glioblastomas and 56% of astrocytomas upregulation of beta-catenin was noted. Our findings on changes of the wnt molecular components contribute to better understanding human astrocytic brain tumors’ genetic profile.

wnt signaling ; astrocytic brain tumors

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