排序方式: 共有49条查询结果,搜索用时 93 毫秒
21.
Julien SG Dubé N Read M Penney J Paquet M Han Y Kennedy BP Muller WJ Tremblay ML 《Nature genetics》2007,39(3):338-346
We investigated the role of protein tyrosine phosphatase 1B (PTP1B) in mammary tumorigenesis using both genetic and pharmacological approaches. It has been previously shown that transgenic mice with a deletion mutation in the region of Erbb2 encoding its extracellular domain (referred to as NDL2 mice, for 'Neu deletion in extracellular domain 2') develop mammary tumors that progress to lung metastasis. However, deletion of PTP1B activity in the NDL2 transgenic mice either by breeding with Ptpn1-deficient mice or by treatment with a specific PTP1B inhibitor results in significant mammary tumor latency and resistance to lung metastasis. In contrast, specific overexpression of PTP1B in the mammary gland leads to spontaneous breast cancer development. The regulation of ErbB2-induced mammary tumorigenesis by PTB1B occurs through the attenuation of both the MAP kinase (MAPK) and Akt pathways. This report provides a rationale for the development of PTP1B as a new therapeutic target in breast cancer. 相似文献
22.
Cell-specific and lamin-dependent targeting of novel transmembrane proteins in the nuclear envelope 总被引:1,自引:1,他引:0
Poonam Malik Nadia Korfali Vlastimil Srsen Vassiliki Lazou Dzmitry G. Batrakou Nikolaj Zuleger Deirdre M. Kavanagh Gavin S. Wilkie Martin W. Goldberg Eric C. Schirmer 《Cellular and molecular life sciences : CMLS》2010,67(8):1353-1369
Nuclear envelope complexity is expanding with respect to identification of protein components. Here we test the validity of
proteomics results that identified 67 novel predicted nuclear envelope transmembrane proteins (NETs) from liver by directly
comparing 30 as tagged fusions using targeting assays. This confirmed 21 as NETs, but 4 only targeted in certain cell types,
underscoring the complexity of interactions that tether NETs to the nuclear envelope. Four NETs accumulated at the nuclear
rim in normal fibroblasts but not in fibroblasts lacking lamin A, suggesting involvement of lamin A in tethering them in the
nucleus. However, intriguingly, for the NETs tested alternative mechanisms for nuclear envelope retention could be found in
Jurkat cells that normally lack lamin A. This study expands by a factor of three the number of liver NETs analyzed, bringing
the total confirmed to 31, and shows that several have multiple mechanisms for nuclear envelope retention. 相似文献
23.
Ferrante MI Zullo A Barra A Bimonte S Messaddeq N Studer M Dollé P Franco B 《Nature genetics》2006,38(1):112-117
The oral-facial-digital type I (OFD1) syndrome (OMIM 311200) is a human developmental disorder; affected individuals have craniofacial and digital abnormalities and, in 15% of cases, polycystic kidney. The disease is inherited as an X-linked dominant male-lethal trait. Using a Cre-loxP system, we generated knockout animals lacking Ofd1 and reproduced the main features of the disease, albeit with increased severity, possibly owing to differences of X inactivation patterns between human and mouse. We found failure of left-right axis specification in mutant male embryos, and ultrastructural analysis showed a lack of cilia in the embryonic node. Formation of cilia was defective in cystic kidneys from heterozygous females, implicating ciliogenesis as a mechanism underlying cyst development. In addition, we found impaired patterning of the neural tube and altered expression of the 5' Hoxa and Hoxd genes in the limb buds of mice lacking Ofd1, suggesting that Ofd1 could have a role beyond primary cilium organization and assembly. 相似文献
24.
Torgerson DG Ampleford EJ Chiu GY Gauderman WJ Gignoux CR Graves PE Himes BE Levin AM Mathias RA Hancock DB Baurley JW Eng C Stern DA Celedón JC Rafaels N Capurso D Conti DV Roth LA Soto-Quiros M Togias A Li X Myers RA Romieu I Van Den Berg DJ Hu D Hansel NN Hernandez RD Israel E Salam MT Galanter J Avila PC Avila L Rodriquez-Santana JR Chapela R Rodriguez-Cintron W Diette GB Adkinson NF Abel RA Ross KD Shi M Faruque MU Dunston GM Watson HR Mantese VJ Ezurum SC Liang L Ruczinski I Ford JG 《Nature genetics》2011,43(9):887-892
Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 × 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma. 相似文献
25.
Summary Triphenyltin (fentin) acetate residues on glass resulting from the evaporation of acetonic solutions, turned out to be less toxic on contact and finally non-toxic to houseflies andSpodoptera littoralis larvae with rising concentration. This paradoxical concentration effect may be due to polymerization of the compound in concentrated solutions.Contribution from the ARO, The Volcani Center, 1976 Series, No. 106-E. 相似文献
26.
A gene expression map of human chromosome 21 orthologues in the mouse 总被引:15,自引:0,他引:15
Gitton Y Dahmane N Baik S Ruiz i Altaba A Neidhardt L Scholze M Herrmann BG Kahlem P Benkahla A Schrinner S Yildirimman R Herwig R Lehrach H Yaspo ML;HSA expression map initiative 《Nature》2002,420(6915):586-590
The DNA sequence of human chromosome 21 (HSA21) has opened the route for a systematic molecular characterization of all of its genes. Trisomy 21 is associated with Down's syndrome, the most common genetic cause of mental retardation in humans. The phenotype includes various organ dysmorphies, stereotypic craniofacial anomalies and brain malformations. Molecular analysis of congenital aneuploidies poses a particular challenge because the aneuploid region contains many protein-coding genes whose function is unknown. One essential step towards understanding their function is to analyse mRNA expression patterns at key stages of organism development. Seminal works in flies, frogs and mice showed that genes whose expression is restricted spatially and/or temporally are often linked with specific ontogenic processes. Here we describe expression profiles of mouse orthologues to HSA21 genes by a combination of large-scale mRNA in situ hybridization at critical stages of embryonic and brain development and in silico (computed) mining of expressed sequence tags. This chromosome-scale expression annotation associates many of the genes tested with a potential biological role and suggests candidates for the pathogenesis of Down's syndrome. 相似文献
27.
Auwerx J Avner P Baldock R Ballabio A Balling R Barbacid M Berns A Bradley A Brown S Carmeliet P Chambon P Cox R Davidson D Davies K Duboule D Forejt J Granucci F Hastie N de Angelis MH Jackson I Kioussis D Kollias G Lathrop M Lendahl U Malumbres M von Melchner H Müller W Partanen J Ricciardi-Castagnoli P Rigby P Rosen B Rosenthal N Skarnes B Stewart AF Thornton J Tocchini-Valentini G Wagner E Wahli W Wurst W 《Nature genetics》2004,36(9):925-927
The European Mouse Mutagenesis Consortium is the European initiative contributing to the international effort on functional annotation of the mouse genome. Its objectives are to establish and integrate mutagenesis platforms, gene expression resources, phenotyping units, storage and distribution centers and bioinformatics resources. The combined efforts will accelerate our understanding of gene function and of human health and disease. 相似文献
28.
Evolution of genes and genomes on the Drosophila phylogeny 总被引:2,自引:0,他引:2
Drosophila Genomes Consortium Clark AG Eisen MB Smith DR Bergman CM Oliver B Markow TA Kaufman TC Kellis M Gelbart W Iyer VN Pollard DA Sackton TB Larracuente AM Singh ND Abad JP Abt DN Adryan B Aguade M Akashi H Anderson WW Aquadro CF Ardell DH Arguello R Artieri CG Barbash DA Barker D Barsanti P Batterham P Batzoglou S Begun D Bhutkar A Blanco E Bosak SA Bradley RK Brand AD Brent MR Brooks AN Brown RH Butlin RK Caggese C Calvi BR Bernardo de Carvalho A Caspi A Castrezana S Celniker SE 《Nature》2007,450(7167):203-218
Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species. 相似文献
29.
Inherited susceptibility to lung cancer may be associated with the T790M drug resistance mutation in EGFR 总被引:9,自引:0,他引:9
Bell DW Gore I Okimoto RA Godin-Heymann N Sordella R Mulloy R Sharma SV Brannigan BW Mohapatra G Settleman J Haber DA 《Nature genetics》2005,37(12):1315-1316
Somatic activating mutations in EGFR identify a subset of non-small cell lung cancer that respond to tyrosine kinase inhibitors. Acquisition of drug resistance is linked to a specific secondary somatic mutation, EGFR T790M. Here we describe a family with multiple cases of non-small cell lung cancer associated with germline transmission of this mutation. Four of six tumors analyzed showed a secondary somatic activating EGFR mutation, arising in cis with the germline EGFR mutation T790M. These observations implicate altered EGFR signaling in genetic susceptibility to lung cancer. 相似文献
30.