Naslov
Interplay between mismatch repair genes and signaling pathways in intracranial meningioma
(Interplay between mismatch repair genes and signaling pathways in intracranial meningioma)

Autori
Bukovac, Anja ; Pećina-Šlaus, Nives ; Kafka, Anja ; Cesarec Augustinović, Sanja ; Raguž, Marina ; Orešković, Darko

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, neobjavljeni rad, znanstveni

Skup
The 7th Mediterranean neuroscience conference

Mjesto i datum
Marakeš, Maroko, 23.06.2019. - 27.06.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
mismatch repair ; Wnt signaling ; EMT ; meningioma

Sažetak
Intracranial meningioma are primary brain tumors with broad spectrum of clinical characteristics and there is considerable variability in the biological behaviour within each of the three tumour grades. Studying molecular characteristics of these tumours may be clinically important because it can reveal patterns of malignant development and valuable biomarkers of tumor progression. Pathways often involved in development of different types of tumors are WNT signaling pathway and epithelial to mesenchymal transition (EMT) with malfunction of p53 tumor suppressor gene and mismatch repair system. In our research, we studied these cellular events and their functionality by analyzing their main effector molecules: p53 (TP53), beta-catenin, E- cadherin (CDH1), MLH1 and MSH2. Genetic changes in TP53, CDH1 and molecules involved in mismatch repair system – MLH1 and MSH2 were analyzed by PCR/RFLP, followed by electrophoresis on Spreadex gels. To assess expression and localization of E- cadherin, beta-catenin and p53, we used DAB- labelled immunohistochemical reaction (EnVisionTM, Dako REALTM) and monoclonal antibody for each protein. In the analyzed meningiomas the levels of the p53 and beta-catenin were significantly negatively correlated (P=0, 002). Also, the expression of p53 was significantly (P=0, 021) associated to higher meningioma grades (II and III) while beta-catenin's upregulation was not associated to malignancy grades. Strong correlation was found in genetic changes of CDH1 and both MLH1 and MSH2 genes (χ2=0, 007 and χ2=0, 037). Our results indicate that meningiomas with lost p53 upregulate beta-catenin and activate WNT signaling. Also, they suggest that loss of function in mismatch repair genes stimulate EMT through loss of E-cadherin.

Izvorni jezik
Engleski

Znanstvena područja
Biologija, Interdisciplinarne prirodne znanosti

POVEZANOST RADA