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Turkish Journal of Medical Sciences

Author ORCID Identifier

BUSE TUREGUN ATASOY: 0000-0002-8328-7291

FİKRET SAHIN, ŞAHİN: 0009-0008-9344-5231

DOI

10.55730/1300-0144.5919

Abstract

Background/aim: The p53 protein, a crucial tumor suppressor, governs cell cycle regulation and apoptosis. Similarly, p63, a member of the p53 family, exhibits traits of both tumor suppression and oncogenic behavior through its isoforms. However, the functional impact of ΔNp63β, an isoform of the p63 protein, on human glioma cancer cells like T98G cells remains poorly understood, representing the novelty of this study in the current literature.Materials, methods: Employing the pRetroX-Tet-On vector system, we investigated ΔNp63β's apoptotic effects on T98G cell lines and assessed its influence on the cell cycle. Initially, we established a rtTA-expressing vector, a component of the pRetroX-Tet-On system, in T98G cell lines. Subsequently, the ΔNp63β cDNA was cloned into the Retropur Tight retroviral vector and transfected into T98G cells containing the pRetroX-Tet-On system for functional analysis. We evaluated gene expression and cell cycle regulation through RT-PCR and flow cytometry, determining protein translation via western blotting. MTT analysis and β-galactosidase cell staining were employed to assess ΔNp63β's cytotoxicity and senescence, respectivelyResults: Overexpression of ΔNp63β in T98G cells correlated with increased cellular proliferation and altered cell cycle regulation, notably upregulating p21 expression independent of p53. Caspase 3/7 activity analyses showed no changes in apoptotic genes but revealed an increase in antiapoptotic gene expression. Surprisingly, cell death in ΔNp63β-overexpressing T98G cells did not occur through apoptosis as anticipated; instead, it resulted from the cytotoxic effects of ΔNp63β protein..Conclusion: Our research found that Δp63β increased p21 levels, induced cell death, and caused cell cycle arrest at the G1 Phase while exhibiting anti-apoptotic properties and promoting senescence. Unexpectedly, overexpression of Δp63β in T98G cells led to significant cell death, potentially through necrosis rather than apoptosis, suggesting a complex role for Δp63β in cell cycle regulation and tumor suppression.

Keywords

apoptosis, cell signalling, p63, T98G

First Page

1355

Last Page

1368

Creative Commons License

Creative Commons Attribution 4.0 International License
This work is licensed under a Creative Commons Attribution 4.0 International License.

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