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GGTase-I deficiency...
GGTase-I deficiency reduces tumor formation and improves survival in mice with K-RAS-induced lung cancer
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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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- 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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- 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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- Karlsson, Christina, 1956 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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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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- Dalin, Martin, 1982 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Institute of Medicine, Department of Molecular and Clinical Medicine
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Weinbaum, C. (author)
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Casey, P. J. (author)
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- Tarkowski, Andrej, 1951 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning,Institute of Medicine, Department of Rheumatology and Inflammation Research
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- Swolin, Birgitta, 1939 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine
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Young, S. G. (author)
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- Bergö, Martin, 1970 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för invärtesmedicin,Institute of Medicine, Department of Internal Medicine
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(creator_code:org_t)
- 2007
- 2007
- English.
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In: J Clin Invest. - 0021-9738. ; 117:5, s. 1294-304
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Abstract
Subject headings
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- Protein geranylgeranyltransferase type I (GGTase-I) is responsible for the posttranslational lipidation of CAAX proteins such as RHOA, RAC1, and cell division cycle 42 (CDC42). Inhibition of GGTase-I has been suggested as a strategy to treat cancer and a host of other diseases. Although several GGTase-I inhibitors (GGTIs) have been synthesized, they have very different properties, and the effects of GGTIs and GGTase-I deficiency are unclear. One concern is that inhibiting GGTase-I might lead to severe toxicity. In this study, we determined the effects of GGTase-I deficiency on cell viability and K-RAS-induced cancer development in mice. Inactivating the gene for the critical beta subunit of GGTase-I eliminated GGTase-I activity, disrupted the actin cytoskeleton, reduced cell migration, and blocked the proliferation of fibroblasts expressing oncogenic K-RAS. Moreover, the absence of GGTase-I activity reduced lung tumor formation, eliminated myeloproliferative phenotypes, and increased survival of mice in which expression of oncogenic K-RAS was switched on in lung cells and myeloid cells. Interestingly, several cell types remained viable in the absence of GGTase-I, and myelopoiesis appeared to function normally. These findings suggest that inhibiting GGTase-I may be a useful strategy to treat K-RAS-induced malignancies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine (hsv//eng)
Keyword
- Alkyl and Aryl Transferases/antagonists & inhibitors/*deficiency/*genetics
- Animals
- Gene Silencing
- Lung Neoplasms/*enzymology/genetics/mortality/*prevention & control
- Mice
- Survival/*physiology
- ras Proteins/*toxicity
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Sjögren, Anna-Ka ...
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Andersson, Karin ...
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Liu, Meng, 1976
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Cutts, Briony, 1 ...
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Karlsson, Christ ...
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Wahlström, Annik ...
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show more...
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Dalin, Martin, 1 ...
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Weinbaum, C.
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Casey, P. J.
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Tarkowski, Andre ...
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Swolin, Birgitta ...
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Young, S. G.
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Bergö, Martin, 1 ...
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show less...
- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
- Articles in the publication
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J Clin Invest
- By the university
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University of Gothenburg