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The involvement of molecular components of Wnt signaling DVL1 and DVL3 in human glioblastoma.

Glioblastoma are the most aggressive and the most invasive tumors of central nervous system, and are classified as grade IV astrocytoma by the criteria of the WHO. There are specific signalling pathways involved in disease development, among which is Wnt pathway. Dishevelled (DVL) is cytoplasmatic phosphoprotein, who comes first in downstream cascade from receptor Frizzled (Fz) and it is one of the crucial molecules of Wnt signalling pathway. When the signalization mediated by DVL is disrupted, it results in tumor development and progression. In the present study changes of two homolog genes of Dishevelled (DVL1 and DVL3) and their protein expression were investigated in glioblastoma. Genetic changes of DVL1 and DVL3 were tested by PCR/loss of heterozygosity (LOH) method using D1S468 microsatellite marker for DVL1 gene and D36S1262 for DVL3 gene. Protein expressions and localizations were analyzed by immunohistochemistry. The results showed 11% of samples with LOH of the DVL1 gene and 50% of samples with LOH of DVL3 gene. A type of genomic instability - MSI was also detected in 22% cases for DVL1 and 6% for DVL3 gene. For future analysis we also plan to analyse amplification of DVL1 and DVL3. The results on protein expressions of DVL1 and DVL3 showed moderate or strong expression in glioblastoma tissues in 65% and 67% of samples respectively. In a portion of glioblastoma nuclear staining was visible. We believe that genetic changes of DVL1 and DVL3 gene are involved in occurrence of glioblastoma, so our findings contribute to better understanding of human glial brain tumor genetic profile.

wnt signaling pathway; glioblastoma; DVL1; DVL3

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