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p57(Kip2) is a paternally imprinted gene that encodes a potent inhibitor of several cyclin/Cdk complexes. p57(Kip2) is primarily expressed in terminally differentiated cells, associates with G1 Cdks, and can cause cell cycle arrest in G1 phase. To investigate the role of p57(Kip2) in vivo, we have ablated the p57(Kip2) gene by homologous recombination in ES(More)
Conversion of active GTP-bound Ras to its inactive GDP-bound form is catalyzed by GTPase-activating proteins (GAPs). Two mammalian Ras-specific GAPs, p120GAP and neurofibromin, the product of the NF1 tumor suppressor gene, have been previously described. We report here the identification of a new human cDNA clone, IQGAP1, which predicts a 1657-amino acid(More)
Identification of key regulatory kinases in the intestinal epithelium are useful to understand the molecular mechanisms that underlie proliferation and differentiation in cells found in this compartment. We used the polymerase chain reaction (PCR) to amplify the catalytic kinase domain of serine-threonine kinases by employing degenerate primers and then(More)
PURPOSE We investigated the possibility that a significant proportion of children with osteosarcoma harbor germline mutations of the p53 tumor suppressor gene and, therefore, this subgroup of pediatric cancer patients should be considered for large-scale predictive testing. PATIENTS AND METHODS Genomic DNA extracted from peripheral-blood leukocytes from(More)
Inherited mutations of the p53 gene significantly increase the risk of developing diverse malignancies, and germline p53 mutations can be detected by assaying the transcriptional activity of the p53 protein in mammalian cells. Here we describe a method starting with lymphocytes that allows detection of germline p53 mutations by 'functional' analysis of p53(More)
MTS-1 is a candidate tumor suppressor gene on chromosome 9p21-22, a region frequently observed to have loss of heterozygosity in esophagus squamous cell carcinomas and pancreatic ductal adenocarcinomas. In order to determine whether MTS-1 sequences are deleted or mutated in cell lines derived from these cancers, we performed PCR amplification of MTS-1 exons(More)
Germ-line mutations of the tumor-suppressor gene p53 have been observed in some families with the Li-Fraumeni syndrome (LFS), a familial cancer syndrome in which affected relatives develop a diverse set of early-onset malignancies including breast carcinoma, sarcomas, and brain tumors. The analysis of the p53 gene in LFS families has been limited, in most(More)
Increasing evidence indicates that p53 is a transcriptional trans-activator through its sequence-specific DNA binding domain. Tumor-derived p53 mutations disrupt the trans-activation ability mainly due to loss of its sequence-specific DNA binding. Using both yeast and mammalian cell assays, the effect of p53 mutations in the carboxy terminal portion was(More)
Pancreatic adenocarcinoma involves activation of the Ki-ras oncogene, inactivation of the p53 tumor suppressor gene, and dysregulation of growth factors and perhaps metastasis genes. Ki-ras oncogene point mutations are known to be involved in pancreatic oncogenesis. The p53 tumor suppressor gene product plays a critical role in cell cycle regulation and(More)
Cardiomyocytes are quite resistant to gene transfer using standard techniques. We developed an expression vector carrying an attenuated but infectious and replicative coxsackievirus B3 (CVB3) genome, and unique ClaI-StuI cloning sites for an exogenous gene, whose product can be released from the nascent viral polyprotein by 2A(pro) cleavage. This vector was(More)