Deletion and transfection analysis of the p15/MTS2 gene in malignant gliomas.
We have investigated the status of the MTS2 gene, encoding the cyclin-dependent kinase (CDK) inhibitor p15, in 32 glioblastomas. Semi-quantitative PCR identified 7 tumors in which the amplified material was 18.6% of controls and 7 in which was 48.0%, suggesting the occurrence of homozygous and hemizygous deletions, respectively. Single strand conformation polymorphism analysis identified one polymorphism but no mutations. We also expressed MTS2 and MTS1, encoding the contiguous and highly homologous CDK inhibitor p16, in U-87 human glioblastoma cells. Both genes, either separately or in combination, inhibit significantly the proliferation rate of U-87 cells but such inhibition is progressively lost. As a whole, the data assign a tumor suppressor role to p15 and confirm homozygous deletions as the favorite mechanism for the inactivation of MTS1 and MTS2 in glioblastomas.
Tenan
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Istituto Nazionale Neurologico Carlo Besta, Department of Biochemistry and Genetics, Milano, Italy.
Benedetti
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Finocchiaro
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D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002460:Cell Line; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D017931:DNA Primers / Q000235:genetics; D004273:DNA, Neoplasm / Q000235:genetics; D004791:Enzyme Inhibitors; D017353:Gene Deletion; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics*; D006720:Homozygote; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D014162:Transfection; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D017931:DNA Primers; D004273:DNA, Neoplasm; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins; D018844:Cyclin-Dependent Kinases