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GDNF family receptor alpha 2 promotes neuroblastoma cell proliferation by interacting with PTEN

Author:
Li, Zuoqing, Xie, Juntao, Fei, Yingchun, Gao, Pengfei, Xie, Qigen, Gao, Wenzong, Xu, Zhe
Source:
Biochemical and biophysical research communications 2019 v.510 no.3 pp. 339-344
ISSN:
0006-291X
Subject:
animal tissues, cell proliferation, childhood, enzyme activity, luciferase, neoplasms, phosphatidylinositol 3-kinase, prognosis, protein-serine-threonine kinases, transcription (genetics)
Abstract:
Neuroblastoma is a childhood tumor, and high-stage neuroblastoma has a poor prognosis. The regulatory mechanisms for neuroblastoma progression are poorly understood. In present study, we found that GDNF family receptor alpha 2 (GFRA2) was upregulated in neuroblastoma cells and tissues, and its overexpression promoted neuroblastoma cell proliferation, as revealed using colony formation, soft agar growth, and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays Tumor suppressor phosphatase and tensin homolog (PTEN) is an inhibitor of the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT serine/threonine kinase (AKT) pathway that interacts with GFRA2. A luciferase activity assay showed GFRA2 inhibits the transcriptional activity of the forkhead box O (FOXO) family proteins, which suggested that GFRA2 activated the PI3K/AKT pathway. Inhibition of the PI3K/AKT pathway in GFRA2 overexpressing cells decreased cell proliferation, confirming that GFRA2 promoted neuroblastoma cell proliferation by activating the PI3K/AKT pathway. In summary, cell proliferation via the GFRA2-PTEN-PI3K/AKT axis may represent new target to develop treatments for neuroblastoma.
Agid:
6280595