AXIN1 Expression and Localization in Meningiomas and Association to Changes of APC and E-cadherin
Nives Pećina-Šlaus1, Anja Kafka2, Tomislav Vladušić3
1Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine University of Zagreb, Zagreb, Croatia Department of Biology, School of Medicine, University of Zagreb, Zagreb, Croatia nina@mef.hr.
Background/Aim:
Tumor suppressor gene AXIN1 is an inhibitor of Wnt signaling pathway. It down-regulates the pathway's main signaling effector molecule, beta-catenin, in an AXIN-based destruction complex. In the present study we investigated the involvement of AXIN1 in intracranial meningioma.
Materials And Methods:
Loss of heterozygosity and microsatellite instability analyses were performed. The consequences of genetic changes on protein expression levels were studied in the same patients by immunohistochemistry.
Results:
Allelic deletions of AXIN1 gene were found in 21.1% of meningiomas. Microsatellite instability was also observed in 5.3% of cases. Weak or lack of AXIN1 expression was found in 21.9% of meningiomas. We found strong statistical correlations between cytoplasmic localization of AXIN1 and its weak expression and also between the simultaneous cytoplasmic and nuclear localizations and moderate and strong expression levels (p<0.000). The findings on AXIN1 were compared to concomitant expression of APC, beta-catenin and E-cadherin in the same patients by Chi-Square tests and Pearson's correlations. Analysis revealed that AXIN1 genetic changes were significantly associated to lack of the expression of APC and presence of mutant APC proteins (p<0.018). Moderate and strong cytoplasmic and nuclear AXIN1 expressions were positively correlated to strong expression of E-cadherin (p<0.05).
Conclusion:
Our findings on genetic changes and expression levels of AXIN1 bring novel data on its involvement in meningeal brain tumors and reveal AXIN1's relation to specific Wnt molecules.
Insights
Genetic alterations and altered expression of the AXIN1 tumor suppressor gene are implicated in intracranial meningiomas. These changes correlate with Wnt pathway molecules, impacting tumor development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- AXIN1 acts as a tumor suppressor by inhibiting the Wnt signaling pathway.
- It down-regulates beta-catenin via an AXIN-based destruction complex.
- The role of AXIN1 in intracranial meningioma remains to be fully elucidated.
Purpose of the Study:
- To investigate the involvement of AXIN1 in intracranial meningioma.
- To analyze genetic alterations and protein expression of AXIN1 in meningiomas.
- To correlate AXIN1 alterations with Wnt pathway components.
Main Methods:
- Loss of heterozygosity and microsatellite instability analyses were performed on meningioma samples.
- Immunohistochemistry was used to assess AXIN1 protein expression and localization.
- Statistical analyses (Chi-Square, Pearson's correlations) compared AXIN1 findings with APC, beta-catenin, and E-cadherin expression.
Main Results:
- Allelic deletions of AXIN1 occurred in 21.1% of meningiomas; microsatellite instability in 5.3%.
- Weak or absent AXIN1 expression was observed in 21.9% of tumors.
- AXIN1 genetic changes correlated with lack of APC expression and presence of mutant APC proteins, and with E-cadherin expression.
Conclusions:
- Genetic alterations and altered expression of AXIN1 are involved in meningioma pathogenesis.
- AXIN1's relationship with specific Wnt pathway molecules, including APC and E-cadherin, is highlighted.
- These findings provide novel insights into the molecular mechanisms of meningeal brain tumors.
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