Statins are lipid-lowering drugs that may help limit cancer occurrence in humans. They drive blockage of the mevalonate pathway, trigger cancer cell apoptosis in vitro and reduce tumour incidence in animals. We have shown in the present study that statins induced apoptosis in HGT-1 human gastric cancer cells, and this was prevented by intermediates of the cholesterol synthetic pathway. In addition, similarly to what we have reported previously for caspase 2 [Logette, Le Jossic-Corcos, Masson, Solier, Sequeira-Legrand, Dugail, Lemaire-Ewing, Desoche, Solary and Corcos (2005) Mol. Cell. Biol. 25, 9621–9631], caspase 7 may also be induced by statins and is under the positive control of SREBP (sterol-regulatory-element-binding protein)-1 and -2, major activators of cholesterol and fatty acid synthesis genes, in HGT-1 cells. Knocking down these proteins strongly reduced caspase 7 mRNA and protein expression, and chromatin immunoprecipitation analyses showed that the proximal promoter region of the CASP7 gene could bind either SREBP-1 or -2. Strikingly, cells selected to grow in the continuous presence of statins showed increased expression of caspase 7 mRNA and protein, which was maintained in the absence of statins for several weeks, suggesting that high expression of this caspase might participate in adaptation to blunting of the mevalonate pathway in this model. Taken together, our results show that caspase 7, as an SREBP-1/2 target, can be induced under mevalonate-restricting conditions, which might help overcome its shortage.
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Research Article|
May 27 2009
Human caspase 7 is positively controlled by SREBP-1 and SREBP-2
Laure Gibot;
Laure Gibot
*INSERM, UMR 613, ECLA team, IFR 148, Université de Brest, 22 Avenue Camille Desmoulins, 29238 Brest Cedex 3, France
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Julie Follet;
Julie Follet
*INSERM, UMR 613, ECLA team, IFR 148, Université de Brest, 22 Avenue Camille Desmoulins, 29238 Brest Cedex 3, France
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Jean-Philippe Metges;
Jean-Philippe Metges
*INSERM, UMR 613, ECLA team, IFR 148, Université de Brest, 22 Avenue Camille Desmoulins, 29238 Brest Cedex 3, France
†Department of Medical Oncology, Centre Hospitalier Universitaire Cavale Blanche et Morvan, Brest 29200, France
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Pierrick Auvray;
Pierrick Auvray
‡C.RIS Pharma, Parc Technopolitain Atalante Saint-Malo, Saint-Malo 35400, France
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Brigitte Simon;
Brigitte Simon
1
*INSERM, UMR 613, ECLA team, IFR 148, Université de Brest, 22 Avenue Camille Desmoulins, 29238 Brest Cedex 3, France
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Laurent Corcos;
Laurent Corcos
*INSERM, UMR 613, ECLA team, IFR 148, Université de Brest, 22 Avenue Camille Desmoulins, 29238 Brest Cedex 3, France
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Catherine Le Jossic-Corcos
*INSERM, UMR 613, ECLA team, IFR 148, Université de Brest, 22 Avenue Camille Desmoulins, 29238 Brest Cedex 3, France
2To whom correspondence should be addressed (email catherine.corcos@univ-brest.fr).
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Publisher: Portland Press Ltd
Received:
October 09 2008
Revision Received:
March 04 2009
Accepted:
March 25 2009
Accepted Manuscript online:
March 25 2009
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 420 (3): 473–483.
Article history
Received:
October 09 2008
Revision Received:
March 04 2009
Accepted:
March 25 2009
Accepted Manuscript online:
March 25 2009
Citation
Laure Gibot, Julie Follet, Jean-Philippe Metges, Pierrick Auvray, Brigitte Simon, Laurent Corcos, Catherine Le Jossic-Corcos; Human caspase 7 is positively controlled by SREBP-1 and SREBP-2. Biochem J 15 June 2009; 420 (3): 473–483. doi: https://doi.org/10.1042/BJ20082057
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