Naslov
Molecular components of the wnt signaling are changed in meningioma

Autori
Pećina-Šlaus, Nives

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

Izvornik
Target Meeting´s 1st World Genetics & genomics Online Conference : conference handbook / Ma, Frank - Bellaire, 2012

Skup
World Genetics & genomics Online Conference (1 ; 2012)

Mjesto i datum
Sjedinjene Američke Države, 17.05.2012. - 19.05.2012

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
wnt signaling; meningioma

Sažetak
The malfunctioning of wnt signal transduction pathway is responsible for tumorigenesis in many different tissues. Our group was studying molecular components of wnt signaling, namely, APC, beta-catenin and E-cadherin in meningiomas, since the molecular mechanisms and candidate genes involved in development of meningiomas still need investigation and elucidation. The main signaling molecule of the pathway is β-catenin, but APC is a critical component of its destruction machinery, while E-cadherin is indirect modulator of the pathway connected also to the adherens junctions. Gene changes were tested by polymerase chain reaction/loss of heterozygosity (LOH) using Restriction Fragment Length Polymorphism (RFLP) method and MSI analysis. Protein expression was analyzed by immunohistochemistry. The analysis regarding APC gene demonstrated LOH in 47% of investigated patients. Immunostaining showed that samples with LOHs were accompanied with the absence of APC protein expression or presence of mutant APC proteins (2 =13.81, df = 2, P0.001). We also showed that nuclear localization of beta-catenin correlates to APC genetic changes (2 =21, 96, df = 2, P0.0001). When investigating E-cadherin’s changes in meningiomas, 32% of investigated samples harbored LOH of this tumor suppressor gene. Moreover MSI was detected in 11% of meningioma cases. Immunostaining showed that overall 73% of samples had downregulation of E-cadherin expression. Intense downregulation of E-cadherin was noticed in tumors with grades II and III. We also noticed that 36.4% of samples with lower E-cadherin expression had beta-catenin located in the nucleus. Also, 75% of samples with genetic changes had beta-catenin in the nucleus. Our findings demonstrated that there is significant association between the genetic changes of CDH1 and the nuclear localization of beta-catenin protein (2 =5.25, df =1. P0.022). Beta-catenin was progressively upregulated from meningothelial to atypical, while 60% of anaplastic showed upregulation and nuclear localization of the protein. Our investigation indicates that changes of wnt signaling molecular components play a role in meningioma formation.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti

POVEZANOST RADA