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MCL-1 dependency of...
MCL-1 dependency of cisplatin-resistant cancer cells
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- Michels, Judith (författare)
- Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
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- Obrist, Florine (författare)
- Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France; Université Paris Sud, Villejuif, France
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- Vitale, Ilio (författare)
- Regina Elena National Cancer Institute, Rome, Italy
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- Lissa, Delphine (författare)
- Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
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- Garcia, Pauline (författare)
- Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
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- Behnam-Motlagh, Parviz (författare)
- Umeå universitet,Klinisk kemi
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- Kohno, Kimitoshi (författare)
- Department of Molecular Biology, School of Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan
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- Wu, Gen Sheng (författare)
- Department of Oncology and Pathology, School of Medicine, Wayne State University, MI, Detroit, United States
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- Brenner, Catherine (författare)
- U769, INSERM-LabEx LERMIT, Faculté de Pharmacie, Châtenay Malabry, France
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- Castedo, Maria (författare)
- Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France
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- Kroemer, Guido (författare)
- Equipe 11 Labellisée Par la Ligue Nationale Contre le Cancer, Centre de Recherche des Cordeliers, INSERM U1138, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France; Metabolomics and Cell Biology Platforms, Gustave Roussy, Villejuif, France; Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP, Paris, France
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(creator_code:org_t)
- Elsevier, 2014
- 2014
- Engelska.
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Ingår i: Biochemical Pharmacology. - : Elsevier. - 0006-2952 .- 1356-1839. ; 92:1, s. 55-61
- Relaterad länk:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- The selection of human cancer cell lines in cis-diamminedichloroplatinum(II) (CDDP, best known as cisplatin) is accompanied by stereotyped alterations that contribute to the acquisition of a CDDP-resistant state. Thus, CDDP resistance often leads to the upregulation of the DNA repair enzyme poly (ADP-ribose) polymerase-1 (PARP1) with the consequent intracellular accumulation of poly (ADP-ribose) (PAR)-modified proteins. Here we report another frequent alteration accompanying CDDP resistance, namely upregulation of the antiapoptotic BCL-2 family protein MCL-1. Six out of 8 CDDP resistant cancer cell lines manifested an increase in MCL-1 protein expression level, while only a minority of cell lines overexpressed BCL-2 or BCL-XL. BCL-XL was decreased in six out of 8 cancer cell lines. Importantly, MCL-1 overexpressing, CDDP resistant cells appear to be 'addicted' to MCL-1 because they died upon depletion of MCL-1 by RNA interference or pharmacological inhibition of MCL-1 expression by the BH3 mimetic obatoclax. Knockdown of PARP1 did not succeed in reducing MCL-1 expression, while depletion or inhibition of MCL-1 failed to affect the activity of PARP1. Hence, the two resistance mechanisms are not linked to each other by a direct cause-effect relationship. Importantly, CDDP-resistant, MCL-1 overexpressing human non-small cell lung cancers responded to monotherapy with obatoclax in vivo, in xenotransplanted mice, underscoring the probable therapeutic relevance of these findings.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Apoptosis
- Chemoresistance
- MCL-1
- Obatoclax
- PARP1
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Michels, Judith
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Obrist, Florine
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Vitale, Ilio
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Lissa, Delphine
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Garcia, Pauline
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Behnam-Motlagh, ...
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Kohno, Kimitoshi
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Wu, Gen Sheng
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Brenner, Catheri ...
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Castedo, Maria
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Kroemer, Guido
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