engleski

Wnt signaling in tumorigenesis of astrocytic brain tumors

Wnt pathway has been established as one of the basic signaling pathways whose malfunctioning often governs tumorigenesis. Investigations on key players of the Wnt signaling: beta-catenin (CTNNB1), TCF1, LEF1, SFRP3, SFRP1 and DVL3 are here presented. We have found that beta-catenin was upregulated in 50% of investigated glioblastomas while its nuclear localization was observed in 52.1%. Transcription factors of the pathway TCF1 and LEF1 were also upregulated in 51.6% and 71% of glioblastomas, respectively. Discriminant function analysis showed that strong expression levels of LEF1 discriminated between astrocytomas of lower grades and glioblastomas offering LEF1 as a potential progression marker. Promoter methylation of SFRP1 gene was found in 29, 2% of astrocytomas, and was progressively rising in higher grades with the highest distribution found in glioblastoma (P = 0, 066). Cases with methylated SFRP1 expressed less SFRP1 protein than unmethylated ones (P = 0, 013). Furthermore, samples with unmethylated SFRP1 promoter had significantly less beta-catenin (P = 0, 046). SFRP3 protein behaved differently demonstrating decreased nuclear but increased cytoplasmic expression in higher grade astrocytomas. This may suggest that SFRP1 acts as tumor suppressor while SFRP3 acts as an agonist of Wnt signaling promoting invasive behavior. DVL3 expression levels showed significant positive correlation to higher tumor grades (P<0.001). Also significant positive correlation between DVL3 and both TCF1 (P = 0.020) and LEF1 (P = 0.006) was noted. Our findings contribute to better understanding of human glial tumor genetic profile and suggest that Wnt signaling plays important role in its etiology.

Wnt signaling ; astrocytic brain tumors

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