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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Dual role of Sp3 transcription factor as an inducer of apoptosis and a marker of tumour aggressiveness
PLoS ONE, Volume 4, No. 2, Article e4478, Year 2009
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Description
Background: The ambiguous role of transcription factor Sp3 for tumour progression is still debated since it was described as a transcriptional repressor or activator. Here we tried to decipher the molecular mechanisms implicated in Sp3 accumulation observed in aggressive tumours. Methodology: We generated normal and tumour cell lines conditionally expressing Sp3. Cell growth was analyzed in vitro and after inoculation in nude mice. Apoptosis was assessed by pan-caspase activity assays, by counting fragmented nuclei and by determination of caspase 9 cleavage. Gene expression was determined by quantitative PCR. Cleavage by different caspases was performed after in vitro translation of the Sp3 cDNA in the presence of [S35] labelled methionine. Different tumour cell lines and head and neck tumour samples were tested for the presence of Sp3 by western blots. Correlation between Sp3 expression and overall survival has been statistically determined. Principal Findings: Conditional over-expression of Sp3 induces apoptosis and modifies expression of genes implicated in the regulation of cell cycle and pro and anti apoptotic genes. Sp3 over-expression strongly reduces the development of tumours in nude mice confirming its pro-apoptotic potential in vivo. However, cells can survive to apoptosis through selective Sp3 cleavage by caspase. Sp3 induction in established tumours resulted in transient regression then progression. Progression coincides with re-accumulation of the full length form of Sp3. Sp3 is over-expressed in tumour cell lines of different origins. The presence of high levels of the full-length form of Sp3 indicates a poor prognosis for overall survival of patients with head and neck tumours. Conclusions: Full length Sp3 accumulation highlights bypass of tumour cell apoptotic capacities and is indicative of head and neck tumours aggressiveness. © 2009 Essafi-Benkhadir et al.
Authors & Co-Authors
Essafi-Benkhadir, Khadija
France, Nice
Université Côte D'azur
Tunisia, Tunis
Institut Pasteur de Tunis
Grosso, Sébastien
France, Nice
Université Côte D'azur
Puissant, Alexandre
France, Nice
Université Côte D'azur
Robert, Guillaume
France, Nice
Université Côte D'azur
Essafi, Makram
France, Nice
Université Côte D'azur
Deckert, Marcel
France, Nice
Université Côte D'azur
Chamorey, Emmanuel
France, Nice
Centre Antoine Lacassagne
Dassonville, Olivier
France, Nice
Centre Antoine Lacassagne
Milano, Gérard
France, Nice
Centre Antoine Lacassagne
Auberger, Patrick
France, Nice
Université Côte D'azur
Pagès, Gilles
France, Nice
Université Côte D'azur
Statistics
Citations: 31
Authors: 11
Affiliations: 3
Identifiers
Doi:
10.1371/journal.pone.0004478
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Study Approach
Quantitative