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BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells

Oncogene volume 21, pages 6772–6778 (2002)Cite this article

Abstract

The p53-transcriptional target, BTG2TIS21/PC3, was previously identified as an antiproliferative gene. However, the precise biological functions of the protein product remain to be elucidated. BTG2TIS21/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 BTG2TIS21/PC3 is functionally significant during the neuronal differentiation process. To test this hypothesis, a vector that expressed BTG2TIS21/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 BTG2TIS21/PC3 overexpression. Furthermore, an antisense oligonucleotide complementary to BTG2TIS21/PC3 mRNA, which was able to inhibit endogenous BTG2TIS21/PC3 expression, triggered programmed cell death in differentiated PC12 cells. These observations confirm that BTG2TIS21/PC3 expression promotes neuronal differentiation and that it is required for survival of terminally differentiated cells.

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Acknowledgements

We thank MD Reynaud and N Borel for their help in preparing the manuscript. This work was supported by grants from INSERM and Association pour la Recherche sur le Cancer.

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Authors and Affiliations

  1. Département d'Oncologie Fondamentale et Appliquée, INSERM Unité, 453. Centre Léon Bérard, 28 rue Laënnec, Lyon, 69008, France

    Fatiha el-Ghissassi, Sandrine Valsesia-Wittmann, Nicole Falette, Cyril Duriez & Alain Puisieux

  2. Department of Biochemistry, NYU School of Medicine, 550 First Avenue, New York, 10016, NY, USA

    Paul D Walden

  3. Department of Urology, NYU School of Medicine, 550 First Avenue, New York, 10016, NY, USA

    Paul D Walden

  4. Département de Génétique Moléculaire et Biochimie Clinique, Faculté de Pharmacie, Lyon, 69008, France

    Alain Puisieux

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  1. Fatiha el-Ghissassi
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Correspondence to Alain Puisieux.

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el-Ghissassi, F., Valsesia-Wittmann, S., Falette, N. et al. BTG2TIS21/PC3 induces neuronal differentiation and prevents apoptosis of terminally differentiated PC12 cells. Oncogene 21, 6772–6778 (2002). https://doi.org/10.1038/sj.onc.1205888

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