WFRF:(Sayin Volkan I. 1983)
Search: WFRF:(Sayin Volkan I. 1983) > Oncogene-induced se...
- 8 of 30
- Previous record
- Next record
- To hitlist
- Cisowski, JaroslawGothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Sahlgrenska Cancer Center,Institute of Medicine, Department of Molecular and Clinical Medicine (author)
Oncogene-induced senescence underlies the mutual exclusive nature of oncogenic KRAS and BRAF
- Article/chapterEnglish2016
Publisher, publication year, extent ...
- 2015-06-01
- Springer Science and Business Media LLC,2016
Numbers
- LIBRIS-ID:oai:gup.ub.gu.se/233964
- https://gup.ub.gu.se/publication/233964URI
- https://doi.org/10.1038/onc.2015.186DOI
- http://kipublications.ki.se/Default.aspx?queryparsed=id:133140695URI
Supplementary language notes
- Language:English
Part of subdatabase
- SwePubSwePub
Classification
Notes
- KRAS and BRAF are among the most commonly mutated oncogenes in human cancer that contribute to tumorigenesis in both distinct and overlapping tissues. However, KRAS and BRAF mutations are mutually exclusive; they never occur in the same tumor cell. The reason for the mutual exclusivity is unknown, but there are several possibilities. The two mutations could be functionally redundant and not create a selective advantage to tumor cells. Alternatively, they could be deleterious for the tumor cell and induce apoptosis or senescence. To distinguish between these possibilities, we activated the expression of BRAF(V600E) and KRAS(G12D) from their endogenous promoters in mouse lungs. Although the tumor-forming ability of BRAF(V600E) was higher than KRAS(G12D), KRAS(G12D) tumors were larger and more advanced. Coactivation of BRAF(V600E) and KRAS(G12D) markedly reduced lung tumor numbers and overall tumor burden compared with activation of BRAF(V600E) alone. Moreover, several tumors expressed only one oncogene, suggesting negative selection against expression of both. Similarly, expression of both oncogenes in mouse embryonic fibroblasts essentially stopped proliferation. The expression of both oncogenes hyperactivated the MEK-ERK-cyclin D pathway but reduced proliferation by increasing the production of p15, p16 and p19 proteins encoded by the Ink4/Arf locus and thereby increased senescence-associated beta-galactosidase-positive cells. The data suggest that coexpression of BRAF(V600E) and KRAS(G12D) in early tumorigenesis leads to negative selection due to oncogene-induced senescence.
Subject headings and genre
- MEDICIN OCH HÄLSOVETENSKAP Klinisk medicin hsv//swe
- MEDICAL AND HEALTH SCIENCES Clinical Medicine hsv//eng
- human-melanoma
- ras oncogenes
- lung-cancer
- k-ras
- mutations
- pathway
- braf(v600e)
- progression
- nras(q61r)
- activation
Added entries (persons, corporate bodies, meetings, titles ...)
- Sayin, Volkan I.,1983Gothenburg University,Göteborgs universitet,Wallenberglaboratoriet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Wallenberg Laboratory,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xsayvo (author)
- Liu, Meng,1976Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för klinisk kemi och transfusionsmedicin,Institute of Biomedicine, Department of Clinical Chemistry and Transfusion Medicine(Swepub:gu)xliume (author)
- Karlsson, C.Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Sahlgrenska Cancer Center,Institute of Medicine, Department of Molecular and Clinical Medicine (author)
- Bergö, Martin,1970Karolinska Institutet,Gothenburg University,Göteborgs universitet,Institutionen för medicin, avdelningen för molekylär och klinisk medicin,Sahlgrenska Cancer Center,Institute of Medicine, Department of Molecular and Clinical Medicine(Swepub:gu)xbmarl (author)
- Göteborgs universitetInstitutionen för medicin, avdelningen för molekylär och klinisk medicin (creator_code:org_t)
Related titles
- In:Oncogene: Springer Science and Business Media LLC35:10, s. 1328-13330950-92321476-5594
Internet link
- 8 of 30
- Previous record
- Next record
- To hitlist
Find more in SwePub
- By the author/editor
- Cisowski, Jarosl ...
- Sayin, Volkan I. ...
- Liu, Meng, 1976
- Karlsson, C.
- Bergö, Martin, 1 ...
- About the subject
-
- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Clinical Medicin ...
- Articles in the publication
- Oncogene
- By the university
- University of Gothenburg
- Karolinska Institutet
Search outside SwePub
- Extend your search to:
- Google Book Search
- Google Scholar
Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.
- Copyright © LIBRIS - National Library Systems
- LIBRIS.kb.se
