WNT/β-catenin Signaling Pathway and Downstream Modulators in Low- and High-grade Glioma.
WNT/β-catenin Signaling Pathway and Downstream Modulators in Low- and High-grade Glioma.
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DOI：
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发表时间：
2016
影响因子：
2.5
通讯作者：
Tetyana Denysenko;L. Annovazzi;P. Cassoni;A. Melcarne;M. Mellai;D. Schiffer
中科院分区：
文献类型：
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作者：
Tetyana Denysenko;L. Annovazzi;P. Cassoni;A. Melcarne;M. Mellai;D. Schiffer
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.
