R280T mutation of p53 gene promotes proliferation of human glioma cells through GSK-3β/PTEN pathway
Abstract
p53 mutation is associated with "gain-of-function" capabilities of human cancers. We aim to identify p53 mutations in human glioma cells and to explore the potential mechanism for mutant p53-promoted cellular growth. Whole genomic DNA was isolated from SWO-38, a human glioma cell line and amplified for the region of exons 5, 6, and 8 in p53 gene using polymerase chain reaction (PCR). By means of direct sequencing of PCR products and alignment analysis using BLAST database, a mutation of G to C transition at codon 280 of p53 exon 8 (AGA→ACA), i.e. R280T was detected in SWO-38 cells. Knockdown of R280T mutant p53 by RNA interference inhibited the GSK-3β/PTEN associated cell proliferation, and PI3K/Akt but not Wnt/β-catenin signaling pathway was involved in this process. Furthermore, depletion or overexpression of PTEN alone did not affect cell proliferation and cell cycle, implicating the impairment of PTEN function in SWO-38 cells. However, knockdown of both PTEN and p53 mutation could significantly rescue the p53 depletion-mediated growth inhibition, suggesting that the R280T mutation in glioma may promote the proliferation through an underlying mechanism related to PTEN. Our observations indicate that the R280T mutation of p53 regulates the proliferation of human glioma cells related to the GSK-3β/PTEN pathway. These findings provide valuable insights for better understanding the molecular mechanism of uncontrolled growth of glioma cells.
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The R280T mutation along the DNA binding domain promotes proliferation through the GSK-3β/PTEN pathway in glioblastoma cells.
“Also, the role of mut-p53 in proliferation has been examined with the R280T mutation along the DBD promoting proliferation through the GSK-3β/PTEN pathway in GBM cells [99].”
From The p53 Pathway in Glioblastoma (2018) · cites this paper as [99]
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- Authors
- Lin, C., Liang, Y., Zhu, H., Zhang, J., & Zhong, X.
- Affiliations
- Jinan University (CN)
- Corresponding author
- Zhong, Xueyun
- Venue
- Neuroscience Letters
- Publisher
- Elsevier BV
- Published
- 2012-10
- Volume
- 529
- Issue
- 1
- Pages
- 60-65
- ISSN
- 0304-3940 (ISSN-L)
- OpenAlex
- W2067979424
- Cited by
- 22
- References
- 36
- Citations by year
- 2025: 1 · 2023: 1 · 2022: 2 · 2021: 1 · 2020: 3 · 2019: 4 · 2018: 3 · 2017: 1 · 2015: 2 · 2014: 3 · 2013: 1
- FWCI
- 0.95
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Neuroscience Letters (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation (81072059)
- National Natural Science Foundation for Young Scholars (81101652)
- Science and Technology Innovation Key Project of Guangdong Higher Education Institutes (CXZD1110)
- Natural Science Foundation of Guangdong Province (10151063201000059)
- Medical Scientific Research Foundation of Guangdong Province (B2011153)
- Fundamental Research Funds for the Central Universities (21609312)
- Topics
- Health Sciences › Medicine › Oncology › Cancer-related Molecular Pathways
- Health Sciences › Medicine › Genetics › Glioma Diagnosis and Treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- gain-of-function p53, glioma, cell proliferation, GSK3β, PTEN, PI3K/Akt signaling, RNAi knockdown, tumor growth mechanisms
- MeSH terms
- Glycogen Synthase Kinase 3 beta, Glioma, Humans, Mutation, Signal Transduction, Tumor Suppressor Protein p53, Glycogen Synthase Kinase 3, Cell Line, Tumor, Cell Proliferation, PTEN Phosphohydrolase
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