Naslov
Upregulation of key wnt signaling molecules in human astrocytic brain tumors

Autori
Pećina-Šlaus, Nives ; Kafka, Anja ; Tomas, Davor ; Krušlin, Božo

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
European Journal of Human Genetics 22(suppl.1) / Brunner, Han - Milano : Nature publishing group, 2014

Skup
The European Human Genetic Conference

Mjesto i datum
Milano, Italija, 31.05.2014. - 03.06.2014

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
wnt signaling pathway; astrocytic brain tumor; CTNNB1; APC; AXIN1; TCF1; LEF1

Sažetak
The knowledge on molecular profiles of astrocytic brain tumors still needs elucidation. In the present study key players of wnt signaling, beta-catenin (CTNNB1), TCF1 and LEF1, adenomatous polyposis coli (APC) and axin (AXIN1) were investigated in the set of human astrocytic brain tumors. The investigation of beta-catenin demonstrated 10% of samples with potential activating mutations. The results on protein levels demonstrated that 50% of glioblastomas (WHO grade IV) and 56% of astrocytomas (WHO grades II and III) showed upregulation of beta-catenin and nuclear localization was found in 52.1% of glioblastomas. Transcription factors of the wnt pathway were also upregulated. Strong TCF1 and LEF1 expression was observed in 51.6% and 71% of glioblastomas. Analysis of variances performed on the total sample indicated significant differences in the values of TCF1 weak expression (F=2.804 ; p=0.045), LEF1 weak (F=4.255 ; p=0.008) and LEF1 strong expression (F=5.498 ; p=0.002) with regard to malignancy grade. The F–ratios for two variables (LEF1 strong and LEF1 weak) indicated that differences between astrocytomas (II, III) and glioblastomas were statistically significant (p<0.02). Allelic losses of APC gene were frequent with glioblastomas showing 60% and diffuse astocytomas (grade II) 20%. Allelic losses of AXIN1 were found in 10% of glioblastomas. In 31% of glioblastomas and 22% of astrocytomas downregulation of axin proteins was detected. In 31% of glioblastomas axin was localized in the nucleus. Our findings contribute to understanding of human astrocytic brain tumor genetic profile and suggest that molecular changes of wnt signaling play important roles in astrocytic tumor etiology.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA