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Inactivating Icmt a...
Inactivating Icmt ameliorates K-RAS-induced myeloproliferative disease.
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- Wahlström, Annika, 1975 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Cutts, Briony, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Liu, Meng, 1976 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Lindskog, Annika, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Karlsson, Christin, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Sjögren, Anna-Karin, 1980 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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- Andersson, Karin, 1972 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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Young, Stephen G (author)
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- Bergö, Martin, 1970 (author)
- Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för invärtesmedicin,Wallenberg Laboratory,Institute of Medicine, Department of Internal Medicine
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(creator_code:org_t)
- American Society of Hematology, 2008
- 2008
- English.
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In: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 112:4, s. 1357-65
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Abstract
Subject headings
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- Hyperactive signaling through the RAS proteins is involved in the pathogenesis of many forms of cancer. The RAS proteins and many other intracellular signaling proteins are either farnesylated or geranylgeranylated at a carboxyl-terminal cysteine. That isoprenylcysteine is then carboxyl methylated by isoprenylcysteine carboxyl methyltransferase (ICMT). We previously showed that inactivation of Icmt mislocalizes the RAS proteins away from the plasma membrane and blocks RAS transformation of mouse fibroblasts, suggesting that ICMT could be a therapeutic target. However, nothing is known about the impact of inhibiting ICMT on the development of malignancies in vivo. In the current study, we tested the hypothesis that inactivation of Icmt would inhibit the development or progression of a K-RAS-induced myeloproliferative disease in mice. We found that inactivating Icmt reduced splenomegaly, the number of immature myeloid cells in peripheral blood, and tissue infiltration by myeloid cells. Moreover, in the absence of Icmt, the ability of K-RAS-expressing hematopoietic cells to form colonies in methylcellulose without exogenous growth factors was reduced dramatically. Finally, inactivating Icmt reduced lung tumor development and myeloproliferation phenotypes in a mouse model of K-RAS-induced cancer. We conclude that inactivation of Icmt ameliorates phenotypes of K-RAS-induced malignancies in vivo.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- Animals
- Lung Neoplasms
- etiology
- prevention & control
- Mice
- Mice
- Knockout
- Myeloid Cells
- pathology
- Myeloproliferative Disorders
- etiology
- pathology
- Protein Methyltransferases
- deficiency
- Proto-Oncogene Proteins p21(ras)
- physiology
- Splenomegaly
Publication and Content Type
- ref (subject category)
- art (subject category)
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Blood
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- By the author/editor
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Wahlström, Annik ...
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Cutts, Briony, 1 ...
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Liu, Meng, 1976
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Lindskog, Annika ...
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Karlsson, Christ ...
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Sjögren, Anna-Ka ...
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show more...
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Andersson, Karin ...
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Young, Stephen G
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Bergö, Martin, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Blood
- By the university
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University of Gothenburg