Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA. Our results not only provide genetic support for the idea that mutations in BRAF and KRAS exert equivalent effects in tumorigenesis, but also emphasize the role of repair processes in establishing the mutation spectra that underpin human cancer.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1038/418934a | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Mitogen-activated protein kinase signal transduction in solid tumors.
Asian Pac J Cancer Prev
July 2015
Department of Pathology, the First Affiliated Hospital of Nanchang University E-mail :
Mitogen-activated protein kinase (MAPK) is an important signaling pathway in living beings in response to extracellular stimuli. There are 5 main subgroups manipulating by a set of sequential actions: ERK(ERK1/ ERK2), c-Jun N(JNK/SAPK), p38 MAPK(p38α, p38β, p38γ and p38δ), and ERK3/ ERK4/ ERK5. When stimulated, factors of upstream or downstream change, and by interacting with each other, these groups have long been recognized to be related to multiple biologic processes such as cell proliferation, differentiation, death, migration, invasion and inflammation.
View Article and Find Full Text PDFGraded activation of the MEK1/MT1-MMP axis determines renal epithelial cell tumor phenotype.
Carcinogenesis
December 2011
Department of Medicine, San Francisco Department of Veterans Affairs Medical Center, University of California, San Francisco, CA 94121, USA.
Activation of Raf/Ras/mitogen-activated protein kinase (MEK)/mitogen-activated protein kinase signaling and elevated expression of membrane type-1 matrix metalloproteinase (MT1-MMP) are associated with von Hippel-Lindau gene alterations in renal cell carcinoma. We postulated that the degree of MEK activation was related to graded expression of MT1-MMP and the resultant phenotype of renal epithelial tumors. Madin Darby canine kidney epithelial cells transfected with a MEK1 expression plasmid yielded populations with morphologic phenotypes ranging from epithelial, mixed epithelial/mesenchymal to mesenchymal.
View Article and Find Full Text PDFMitogen-activated protein kinase signaling is activated in prostate tumors but not mediated by B-RAF mutations.
Eur Urol
November 2006
Department of Urology, University of Regensburg, Germany.
Objectives: A dysregulated mitogen-activated protein kinase (MAPK) pathway plays an important role in various malignancies and is often mediated by mutations in several oncogenes (eg, RAF, RAS). B-RAF mutations, predominantly the specific V600E mutation and additional alterations in exons 11 and 15, were frequently detected in malignant melanomas, papillary thyroid tumors, and colorectal cancers with microsatellite instability (MSI). The present study investigated B-RAF mutations, MSI status, and activation of MAPK signaling in prostate tumors.
View Article and Find Full Text PDFInsulin-like growth factor (IGF)-I obliterates the pregnancy-associated protection against mammary carcinogenesis in rats: evidence that IGF-I enhances cancer progression through estrogen receptor-alpha activation via the mitogen-activated protein kinase pathway.
Breast Cancer Res
November 2004
Department of Molecular, Cell, and Developmental Biology, University of California, Santa Cruz, California, USA.
Introduction: Pregnancy protects against breast cancer development in humans and rats. Parous rats have persistently reduced circulating levels of growth hormone, which may affect the activity of the growth hormone/insulin-like growth factor (IGF)-I axis. We investigated the effects of IGF-I on parity-associated protection against mammary cancer.
View Article and Find Full Text PDFTumorigenesis: RAF/RAS oncogenes and mismatch-repair status.
Nature
August 2002
Sidney Kimmel Comprehensive Cancer Centre, Howard Hughes Medical Institution and Program in Cellular and Molecular Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
Genes of the RAF family encode kinases that are regulated by Ras and mediate cellular responses to growth signals. Activating mutations in one RAF gene, BRAF, have been found in a high proportion of melanomas and in a small fraction of other cancers. Here we show that BRAF mutations in colorectal cancers occur only in tumours that do not carry mutations in a RAS gene known as KRAS, and that BRAF mutation is linked to the proficiency of these tumours in repairing mismatched bases in DNA.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!