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Myc sensitizes p53-...
Myc sensitizes p53-deficient cancer cells to the DNA-damaging effects of the DNA methyltransferase inhibitor decitabine
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- Höglund, Andreas, 1980- (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet),Jonas Nilsson
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- Nilsson, Lisa M., 1976- (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
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- Plym Forshell, Linus, 1977- (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
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- Maclean, Kirsteen H. (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
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- Nilsson, Jonas A. (författare)
- Umeå universitet,Institutionen för molekylärbiologi (Teknisk-naturvetenskaplig fakultet)
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(creator_code:org_t)
- The American Society of Hematology, 2009
- 2009
- Engelska.
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Ingår i: Blood. - : The American Society of Hematology. - 0006-4971 .- 1528-0020. ; 113:18, s. 4281-4288
- 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
- Decitabine (also referred to as 5-aza-2'-deoxycytidine) is a drug that has recently been approved by the Food and Drug Administration (FDA) for the treatment of myelodysplastic syndrome (MDS). The mechanism of action is believed to be the blocking of DNA methylation and thereby reactivating silenced genes involved in harnessing MDS. When analyzing reactivation of genes involved in Burkitt lymphoma (BL), we discovered that decitabine also sensitizes tumor cells by inducing DNA damage. This sensitization is grossly augmented by the MYC oncogene, which is overexpressed in BL, and occurs in cells lacking a functional p53 tumor suppressor pathway. In p53-deficient BL cells and p53(-/-) mouse embryo fibroblasts, Myc overrides a transient G2-block exerted by decitabine via activation of Chk1. This triggers aneuploidy and cell death that correlates with, but can occur in the absence of, Epstein-Barr virus (EBV) reactivation, caspase activation, and/or expression of the BH3-only protein Puma. In vivo modeling of Myc-induced lymphoma suggests that decitabine constitutes a potential new drug against lymphoma that would selectively sensitize tumor cells but spare normal tissue.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Nyckelord
- Myc
- Molecular biology
- Molekylärbiologi
- molekylärbiologi
- Molecular Biology
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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