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Forced expression o...
Forced expression of the DEK-NUP214 fusion protein promotes proliferation dependent on upregulation of mTOR
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- Sandén, Carl (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- Ageberg, Malin (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- Petersson, Jessica (författare)
- Lund University,Lunds universitet,Institutionen för immunteknologi,Institutioner vid LTH,Lunds Tekniska Högskola,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Department of Immunotechnology,Departments at LTH,Faculty of Engineering, LTH,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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- Lennartsson, Andreas (författare)
- Karolinska Institutet
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- Gullberg, Urban (författare)
- Lund University,Lunds universitet,Avdelningen för hematologi och transfusionsmedicin,Institutionen för laboratoriemedicin,Medicinska fakulteten,Division of Hematology and Transfusion Medicine,Department of Laboratory Medicine,Faculty of Medicine
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(creator_code:org_t)
- 2013-09-27
- 2013
- Engelska.
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Ingår i: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 13
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Abstract
Ämnesord
Stäng
- Background: The t(6;9)(p23;q34) chromosomal translocation is found in 1% of acute myeloid leukemia and encodes the fusion protein DEK-NUP214 (formerly DEK-CAN) with largely uncharacterized functions. Methods: We expressed DEK-NUP214 in the myeloid cell lines U937 and PL-21 and studied the effects on cellular functions. Results: In this study, we demonstrate that expression of DEK-NUP214 increases cellular proliferation. Western blot analysis revealed elevated levels of one of the key proteins regulating proliferation, the mechanistic target of rapamycin, mTOR. This conferred increased mTORC1 but not mTORC2 activity, as determined by the phosphorylation of their substrates, p70 S6 kinase and Akt. The functional importance of the mTOR upregulation was determined by assaying the downstream cellular processes; protein synthesis and glucose metabolism. A global translation assay revealed a substantial increase in the translation rate and a metabolic assay detected a shift from glycolysis to oxidative phosphorylation, as determined by a reduction in lactate production without a concomitant decrease in glucose consumption. Both these effects are in concordance with increased mTORC1 activity. Treatment with the mTORC1 inhibitor everolimus (RAD001) selectively reversed the DEK-NUP214-induced proliferation, demonstrating that the effect is mTOR-dependent. Conclusions: Our study shows that the DEK-NUP214 fusion gene increases proliferation by upregulation of mTOR, suggesting that patients with leukemias carrying DEK-NUP214 may benefit from treatment with mTOR inhibitors.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Nyckelord
- Acute myeloid leukemia
- DEK-NUP214
- DEK-CAN
- Fusion gene
- Proliferation
- mTOR
- Everolimus
Publikations- och innehållstyp
- art (ämneskategori)
- ref (ämneskategori)
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