Naslov
WNT Signaling in Human Brain Tumors

Autori
Pećina-Šlaus, Nives

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

Izvornik
Abstracts of the 13th World Congress on Advances in Oncology, and 11th International Symposium on Molecular Medicine ; u: International Journal of Molecular Medicine / Spandidos, D.A. - Atena : Spandidos Publications, 2008, S15-S15

Skup
World Congress on Advances in Oncology, and 11th International Symposium on Molecular Medicine (13 ; 2008)

Mjesto i datum
Hersonissos, Grčka; Heraklion, Grčka, 09.10.2008. - 11.10.2008

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
wnt signaling; brain tumors

Sažetak
Genetic profile of human brain tumors is still inadequately explained. Gene instabilities of key players of wnt signaling, adenomatous polyposis coli (APC), axin (AXIN1) and E-cadherin (CDH1) were tested by PCR/loss of heterozygosity (LOH). Beta-catenin (CTNNB1) was investigated by heteroduplex method. Relevant proteins were investigated by immunohistochemistry and Image analysis. Changes of CDH1 gene were found almost exclusively in meningiomas with correlation at 0.002 level. Our analysis showed LOHs of CDH1 gene in 31% of meningiomas examined. Changes of APC gene were more frequent and distributed among different tumor types, with glioblastomas showing the highest percentage. Observed LOHs of APC were distributed to: 60% of glioblastomas, 47% of meningiomas, 20% of astocytomas, and 17% neurinomas. One oligoastrocytoma and medulloblastoma also showed LOH of APC gene. Immunostaining showed that meningioma samples with LOHs were accompanied with the absence of APC protein or presence of mutant APC proteins (P 0.001). We also showed that nuclear localization of beta-catenin correlates to APC genetic changes (P 0.0001). The investigation on beta-catenin demonstrated 10% of heteroduplexes in β -catenin’ s exon 3. We found LOH of AXIN-1 in 6.3% of glioblastomas, 1 LOH in neuroepithelial dysembrioplastic tumor and 1 in medulloblastoma. In 68.8% of samples axin was observed in the cytoplasm, in 28.1% in both cytoplasm and nucleus and 3.1% of tumors had no expression. Beta-catenin was observed mainly in the nucleus or cytoplasm and nucleus (59.4%). Expression in 34.4% of samples was in the cytoplasm and 6.2% showed no expression. Comparison of mean values of relative increase of axin and beta-catenin shows that they are reversely proportional (P=0.014). Moreover, relative quantity of beta-catenin protein in patients with AXIN1 LOH was higher in comparison to patients without LOH (P=0.040). Our findings on changes of the wnt molecular components may contribute to better understanding human brain tumors’ genetic profiles.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA