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Published on: February 13, 2021
BTG2(TIS21/PC3) induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells
Fatiha el-Ghissassi1, Sandrine Valsesia-Wittmann, Nicole Falette
1Département d'Oncologie Fondamentale et Appliquée, INSERM Unité 453. Centre Léon Bérard, 28 rue Laënnec, 69008, Lyon, France.
Abstract:
The p53-transcriptional target, BTG2(TIS21/PC3), was previously identified as an antiproliferative gene. However, the precise biological functions of the protein product remain to be elucidated. BTG2(TIS21/PC3) expression is induced in vivo during neurogenesis, and the gene is transiently expressed in vitro in rat pheochromocytoma PC12 cells after induction of neuronal differentiation by addition of nerve growth factor (NGF). These observations suggest that BTG2(TIS21/PC3) is functionally significant during the neuronal differentiation process. To test this hypothesis, a vector that expressed BTG2(TIS21/PC3) under the control of an inducible promoter was introduced into PC12 cells. Growth arrest and differentiation in response to NGF were greatly enhanced by BTG2(TIS21/PC3) overexpression. Furthermore, an antisense oligonucleotide complementary to BTG2(TIS21/PC3) mRNA, which was able to inhibit endogenous BTG2(TIS21/PC3) expression, triggered programmed cell death in differentiated PC12 cells. These observations confirm that BTG2(TIS21/PC3) expression promotes neuronal differentiation and that it is required for survival of terminally differentiated cells.
Insights
BTG2, a gene targeting p53, promotes neuronal differentiation and survival. Overexpressing BTG2 enhances nerve growth factor-induced differentiation, while inhibiting it causes cell death in differentiated neurons.
Area of Science:
- Neuroscience
- Cell Biology
- Molecular Biology
Background:
- BTG2 (also known as TIS21/PC3) is a p53-transcriptional target previously identified as an antiproliferative gene.
- The specific roles of BTG2 protein in biological processes, particularly neurogenesis, require further investigation.
Purpose of the Study:
- To investigate the functional significance of BTG2 during neuronal differentiation.
- To elucidate the role of BTG2 in the survival of terminally differentiated neuronal cells.
Main Methods:
- Utilized PC12 cells, a rat pheochromocytoma cell line, for in vitro studies.
- Employed a vector for inducible overexpression of BTG2 in PC12 cells.
- Used antisense oligonucleotides to inhibit endogenous BTG2 expression.
Main Results:
- BTG2 overexpression significantly enhanced nerve growth factor (NGF)-induced growth arrest and neuronal differentiation in PC12 cells.
- Inhibition of endogenous BTG2 expression using antisense oligonucleotides led to programmed cell death in differentiated PC12 cells.
Conclusions:
- BTG2 expression plays a crucial role in promoting neuronal differentiation.
- BTG2 is essential for the survival of terminally differentiated neuronal cells.
