气候变化领域集成服务门户(CCPortal): Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells

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DOI	10.1126/science.1174229
	Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells
	Yun J.; Rago C.; Cheong I.; Pagliarini R.; Angenendt P.; Rajagopalan H.; Schmidt K.; Willson J.K.V.; Markowitz S.; Zhou S.; Diaz Jr. L.A.; Velculescu V.E.; Lengauer C.; Kinzler K.W.; Vogelstein B.; Papadopoulos N.
发表日期	2009
ISSN	0036-8075
起始页码	1555
结束页码	1559
卷号	325 期号:5947
英文摘要	Tumor progression is driven by genetic mutations, but little is known about the environmental conditions that select for these mutations. Studying the transcriptomes of paired colorectal cancer cell lines that differed only in the mutational status of their KRAS or BRAF genes, we found that GLUT1, encoding glucose transporter-1, was one of three genes consistently up-regulated in cells with KRAS or BRAF mutations. The mutant cells exhibited enhanced glucose uptake and glycolysis and survived in low-glucose conditions, phenotypes that all required GLUT1 expression. In contrast, when cells with wild-type KRAS alleles were subjected to a low-glucose environment, very few cells survived. Most surviving cells expressed high levels of GLUT1, and 4% of these survivors had acquired KRAS mutations not present in their parents. The glycolysis inhibitor 3-bromopyruvate preferentially suppressed the growth of cells with KRAS or BRAF mutations. Together, these data suggest that glucose deprivation can drive the acquisition of KRAS pathway mutations in human tumors.
英文关键词	adenosine diphosphate; adenosine triphosphate; B Raf kinase; fluorodeoxyglucose f 18; glucose; glucose transporter 1; K ras protein; lactic acid; oxygen; small interfering RNA; transcriptome; allele; cytogenetics; gene expression; glucose; growth rate; mutation; nutrient uptake; phenotype; tumor; allele; article; cancer cell; carcinogenesis; cell growth; cell survival; colorectal cancer; gene expression; gene mutation; gene overexpression; genetic analysis; glucose metabolism; glucose transport; glycolysis; growth inhibition; homologous recombination; human; human cell; hypoglycemia; mismatch repair; mitochondrial respiration; molecular mimicry; nonhuman; oncogene K ras; oxygen consumption; phenotype; positron emission tomography; precancer; priority journal; protein expression; serial analysis of gene expression; upregulation; wild type; Animals; Cell Line, Tumor; Cell Proliferation; Colorectal Neoplasms; Gene Expression Regulation, Neoplastic; Gene Targeting; Genes, ras; Glucose; Glucose Transporter Type 1; Glycolysis; Humans; Lactic Acid; Mice; Mice, Nude; Mutation; Neoplasm Transplantation; Oligonucleotide Array Sequence Analysis; Proto-Oncogene Proteins B-raf; Pyruvates; Transplantation, Heterologous
语种	英语
来源期刊	Science
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/246119
作者单位	Ludwig Center for Cancer Genetics and Therapeutics, Howard Hughes Medical Institute, Johns Hopkins Kimmel Cancer Center, Baltimore, MD 21231, United States; Harold C. Simmons Comprehensive Cancer Center, University of Texas, Southwestern Medical Center, Dallas, TX 75390, United States; Department of Medicine and Ireland Cancer Center, Case Western Reserve University, Hospitals of Cleveland, Cleveland, OH 44106, United States; Novartis Institute for Biomedical Research, Cambridge, MA 02139, United States; Cardiovascular Medicine, Brigham and Women's Hospital, Boston, MA 02115, United States; Sanofi-Aventis, 13 Quai Jules Guesde, 94400 Vitry-sur-Seine, France
推荐引用方式 GB/T 7714	Yun J.,Rago C.,Cheong I.,et al. Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells[J],2009,325(5947).
APA	Yun J..,Rago C..,Cheong I..,Pagliarini R..,Angenendt P..,...&Papadopoulos N..(2009).Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells.Science,325(5947).
MLA	Yun J.,et al."Glucose deprivation contributes to the development of KRAS pathway mutations in tumor cells".Science 325.5947(2009).