|Title||Met proto-oncogene juxtamembrane rare variations in mouse and humans: Differential effects of Arg and Cys alleles on mouse lung tumorigenesis|
|Publication Type||Articolo su Rivista peer-reviewed|
|Year of Publication||2005|
|Authors||Zaffaroni, D., Spinola M., Galvan A., Falvella F.S., Pazzaglia Simonetta, Saran Anna, Mancuso Mariateresa, Galbiati F., Pignatiello C., Cabrera W., Ibanez O., Manenti G., and Dragani T.A.|
|Keywords||adenocarcinoma, allele, Alleles, Amino Acid Sequence, amino acid substitution, animal, animal experiment, animal model, animal tissue, Animals, arginine, article, Carcinoma, Cell Transformation, comparative study, Cysteine, disease model, Disease Models, DNA Mutational Analysis, gene locus, gene product, genetic linkage, genetic predisposition, Genetic Predisposition to Disease, genetics, genomic DNA, Germ-Line Mutation, Growth Factor, growth factor receptor, human, human tissue, Humans, Inbred Strains, Linkage (Genetics), lung cancer, lung carcinogenesis, Lung Neoplasms, lung non small cell cancer, lung tumor, MET protein, Mice, molecular genetics, Molecular Sequence Data, mouse, mouse strain, multifactorial inheritance, mutation, Neoplastic, Non-Small-Cell Lung, nonhuman, nucleotide sequence, oncoprotein, pathophysiology, priority journal, protease-activated receptor 4, protein domain, protein par4, proteinase activated receptor 4, proto oncogene, Proto-Oncogene Proteins, Receptors, Reverse Transcriptase Polymerase Chain Reaction, reverse transcription polymerase chain reaction, scatter factor receptor, Sequence Analysis, sequence homology, Thrombin, thrombin receptor, unclassified drug|
Analysis of seven candidate genes mapping in the 1-Mb region of the mouse pulmonary adenoma resistance 4 (Par4) locus revealed a single amino-acid change, consisting in a nonconservative Arg968Cys variation in the juxtamembrane domain of the Met proto-oncogene-encoded protein. The BALB/c strain (resistant allele) carried the Arg allele, whereas the SWR/J mouse strain (Par4-susceptible allele) carried the Cys variation, recently proven to functionally modulate tumorigenesis. Seven genetic linkage crosses herein analysed and six crosses reported in the literature pointed to the candidacy of the Met gene for Par4. Analysis of genomic DNA of 126 lung adenocarcinoma patients for the Met juxtamembrane domain revealed the same Arg/Cys variation at the mouse homologous position in one patient; two other patients carried additional variants in the same domain, suggesting a potential role for rare MET juxtamembrane variants in human lung cancer. © 2005 Nature Publishing Group All rights reserved.
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