共查询到20条相似文献,搜索用时 156 毫秒
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Ghoussaini M Fletcher O Michailidou K Turnbull C Schmidt MK Dicks E Dennis J Wang Q Humphreys MK Luccarini C Baynes C Conroy D Maranian M Ahmed S Driver K Johnson N Orr N dos Santos Silva I Waisfisz Q Meijers-Heijboer H Uitterlinden AG Rivadeneira F;Netherlands Collaborative Group on Hereditary Breast Ovarian Cancer 《Nature genetics》2012,44(3):312-318
Breast cancer is the most common cancer among women. To date, 22 common breast cancer susceptibility loci have been identified accounting for ~8% of the heritability of the disease. We attempted to replicate 72 promising associations from two independent genome-wide association studies (GWAS) in ~70,000 cases and ~68,000 controls from 41 case-control studies and 9 breast cancer GWAS. We identified three new breast cancer risk loci at 12p11 (rs10771399; P = 2.7 × 10(-35)), 12q24 (rs1292011; P = 4.3 × 10(-19)) and 21q21 (rs2823093; P = 1.1 × 10(-12)). rs10771399 was associated with similar relative risks for both estrogen receptor (ER)-negative and ER-positive breast cancer, whereas the other two loci were associated only with ER-positive disease. Two of the loci lie in regions that contain strong plausible candidate genes: PTHLH (12p11) has a crucial role in mammary gland development and the establishment of bone metastasis in breast cancer, and NRIP1 (21q21) encodes an ER cofactor and has a role in the regulation of breast cancer cell growth. 相似文献
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Locasale JW Grassian AR Melman T Lyssiotis CA Mattaini KR Bass AJ Heffron G Metallo CM Muranen T Sharfi H Sasaki AT Anastasiou D Mullarky E Vokes NI Sasaki M Beroukhim R Stephanopoulos G Ligon AH Meyerson M Richardson AL Chin L Wagner G Asara JM Brugge JS Cantley LC Vander Heiden MG 《Nature genetics》2011,43(9):869-874
Most tumors exhibit increased glucose metabolism to lactate, however, the extent to which glucose-derived metabolic fluxes are used for alternative processes is poorly understood. Using a metabolomics approach with isotope labeling, we found that in some cancer cells a relatively large amount of glycolytic carbon is diverted into serine and glycine metabolism through phosphoglycerate dehydrogenase (PHGDH). An analysis of human cancers showed that PHGDH is recurrently amplified in a genomic region of focal copy number gain most commonly found in melanoma. Decreasing PHGDH expression impaired proliferation in amplified cell lines. Increased expression was also associated with breast cancer subtypes, and ectopic expression of PHGDH in mammary epithelial cells disrupted acinar morphogenesis and induced other phenotypic alterations that may predispose cells to transformation. Our findings show that the diversion of glycolytic flux into a specific alternate pathway can be selected during tumor development and may contribute to the pathogenesis of human cancer. 相似文献
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Cortina C Palomo-Ponce S Iglesias M Fernández-Masip JL Vivancos A Whissell G Humà M Peiró N Gallego L Jonkheer S Davy A Lloreta J Sancho E Batlle E 《Nature genetics》2007,39(11):1376-1383
The genes encoding tyrosine kinase receptors EphB2 and EphB3 are beta-catenin and Tcf4 target genes in colorectal cancer (CRC) and in normal intestinal cells. In the intestinal epithelium, EphB signaling controls the positioning of cell types along the crypt-villus axis. In CRC, EphB activity suppresses tumor progression beyond the earliest stages. Here we show that EphB receptors compartmentalize the expansion of CRC cells through a mechanism dependent on E-cadherin-mediated adhesion. We demonstrate that EphB-mediated compartmentalization restricts the spreading of EphB-expressing tumor cells into ephrin-B1-positive territories in vitro and in vivo. Our results indicate that CRC cells must silence EphB expression to avoid repulsive interactions imposed by normal ephrin-B1-expressing intestinal cells at the onset of tumorigenesis. 相似文献
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The Oct4 and Nanog transcription network regulates pluripotency in mouse embryonic stem cells 总被引:45,自引:0,他引:45
Loh YH Wu Q Chew JL Vega VB Zhang W Chen X Bourque G George J Leong B Liu J Wong KY Sung KW Lee CW Zhao XD Chiu KP Lipovich L Kuznetsov VA Robson P Stanton LW Wei CL Ruan Y Lim B Ng HH 《Nature genetics》2006,38(4):431-440
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Mutations truncating the EP300 acetylase in human cancers 总被引:21,自引:0,他引:21
Gayther SA Batley SJ Linger L Bannister A Thorpe K Chin SF Daigo Y Russell P Wilson A Sowter HM Delhanty JD Ponder BA Kouzarides T Caldas C 《Nature genetics》2000,24(3):300-303