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Overexpression of Sp1 transcription factor induces apoptosis

Oncogene volume 25, pages 7096–7105 (2006)Cite this article

Abstract

Transcription factor Sp1 has recently been shown to be overexpressed in a number of human cancers and its overexpression contributes to malignant transformation. Sp1 regulates the expression of a number of genes participating in multiple aspects of tumorigenesis such as angiogenesis, cell growth and apoptosis resistance. To better understand the role of increased Sp1 levels on apoptosis regulation we have used retroviruses to overexpress this protein in haematopoietic Baf-3 cells and in 3T3 fibroblasts. We have also used inducible expression systems to control ectopic Sp1 levels in different cell types. Surprisingly, Sp1 overexpression on its own induces apoptosis in all the cellular models tested. The apoptotic pathways induced by Sp1 overexpression are cell type specific. Finally, using a truncated form of Sp1, we show that Sp1-induced apoptosis requires its DNA-binding domain. Our results highlight that Sp1 levels in untransformed cells must be tightly regulated as Sp1 overexpression leads to the induction of apoptosis. Our results also suggest that cancer cells overexpressing Sp1 can avoid Sp1-induced apoptosis.

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Acknowledgements

We thank Dr Kahn-Perlès for critical advice and Chantal Bella from the Plateau de Cytométrie (IFR 128) for technical assistance. We thank Dr Arpin for critical reading of the manuscript. This work was supported by grants from the Inserm, Association pour la Recherche contre le Cancer, Ligue du Rhône, Région Rhône-Alpes, Cancéropole national and Université Claude Bernard Lyon 1. ED is supported by a fellowship from the Ligue Nationale contre le Cancer.

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Author notes

  1. E Deniaud and J Baguet: These two authors contributed equally to this work.

Authors and Affiliations

  1. Inserm, U503, Lyon, France

    E Deniaud, J Baguet, A-L Mathieu, J Marvel & Y Leverrier

  2. IFR128, BioSciences Lyon-Gerland, Lyon, France

    E Deniaud, J Baguet, A-L Mathieu, J Marvel & Y Leverrier

  3. Université Lyon 1, Lyon, France

    E Deniaud, J Baguet, A-L Mathieu, J Marvel & Y Leverrier

  4. Centre Antoine Lacassagne, UMR CNRS 6543, Université de Nice Sophia Antipolis, Nice, France

    G Pagès

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  1. E Deniaud
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Correspondence to J Marvel or Y Leverrier.

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Deniaud, E., Baguet, J., Mathieu, AL. et al. Overexpression of Sp1 transcription factor induces apoptosis. Oncogene 25, 7096–7105 (2006). https://doi.org/10.1038/sj.onc.1209696

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