WNT/β-catenin Signaling Pathway and Downstream Modulators in Low- and High-grade Glioma

Cancer Genomics - Proteomics

TETYANA DENYSENKO⁴  ANTONIO MELCARNE²  MARTA MELLAI³  PAOLA CASSONI¹  LAURA ANNOVAZZI³  DAVIDE SCHIFFER³ 

[1] epartment of Medical Sciences, University of Turin/Health and Science City, Turin, Italyepartment of Medical Sciences, University of Turin/Health and Science City, Turin, Italyepartment of Medical Sciences, University of Turin/Health and Science City, Turin, Italy;epartment of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italyepartment of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italyepartment of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italy;esearch Center, Polyclinic of Monza Foundation, Vercelli, Italyesearch Center, Polyclinic of Monza Foundation, Vercelli, Italyesearch Center, Polyclinic of Monza Foundation, Vercelli, Italy;esearch Center, Polyclinic of Monza Foundation, Vercelli, Italyepartment of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italyesearch Center, Polyclinic of Monza Foundation, Vercelli, Italyesearch Center, Polyclinic of Monza Foundation, Vercelli, Italyepartment of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italyepartment of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italyesearch Center, Polyclinic of Monza Foundation, Vercelli, Italyepartment of Neurosurgery, CTO Hospital/Health and Science City, Turin, Italy

关键词: Gliomas;    glioblastoma multiforme;    WNT3a;    β-catenin;    TCF4;    prognosis;   

DOI  :  

来源: Delinasios GJ CO

【 摘 要 】

Background: Aberrant activation of the canonical Wingless-type MMTV integration site family (WNT)/β-catenin signaling pathway is critical for gliomas. Materials and Methods: In 74 gliomas of different histological grade and in 24 glioblastoma cell lines, protein expression of WNT member 3a (WNT3a), β-catenin and transcription factor 4 (TCF4) was investigated by immunohistochemistry, western blotting, immunofluorescence and immunocytochemistry. In tumors and cell lines, WNT3A expression was assessed at the mRNA level by quantitative real-time polymerase chain reaction. Results: WNT3a was overexpressed at the protein and mRNA levels in malignant astrocytic tumors and cell lines. Cytoplasmic expression of β-catenin was detected in high-grade gliomas and cell lines, with evidence of nuclear translocation on fractionated protein extracts. Activating mutations in the β-catenin encoding gene (CTNNB1) were excluded by direct sequencing. TCF4 was statistically correlated with Ki-67/MIB-1 and cyclin D1 labeling indices. Conclusion: Expression of WNT3a, cytoplasmic β-catenin and TCF4 was significantly associated with the histological malignancy grade and with a worse prognosis for patients with glioma.

【 授权许可】

Unknown