Coincidental alterations of p16INK4A/CDKN2 and other genes in human lung cancer cell lines.
Cyclin-dependent kinase (CDK) inhibitor genes have recently been proposed as new tumor suppressor genes. To define the possible participation of CDK inhibitor genes in lung carcinogenesis, we investigated the alterations of p15INK4B, p16INK4A, p21Waf1, and p27Kip1 genes in 34 human lung cancer cell lines using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP), direct sequencing, and southern dot blot methods. Among the four CDK inhibitor genes, alterations of only the p16INK4A gene were found in 8 out of 34 (24%) cell lines, and all eight cell lines having a p16INK4A gene alteration had an alteration of either the K-ras of p53 gene. Conversely, p16INK4A gene alterations were found in none of the 3 cell lines having Rb gene alterations and none of the 3 cell lines having amplification of the N-myc gene. Polymorphism was found in both p21Waf1 and p27Kip1 genes, but no association was found between the polymorphism and alterations of other genes. These results suggest that p16INK4A gene alterations may play a certain role for lung carcinogenesis in co-operation with either K-ras or p53 gene alterations.
First Department of Internal Medicine, Toyama Medical and Pharmaceutical University, Japan.
T
T
Fujishita
Y
Y
Mizushima
T
T
Kashii
M
M
Kobayashi
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D018797:Cell Cycle Proteins; D002460:Cell Line; D003110:Colonic Neoplasms / Q000235:genetics; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics*; D050759:Cyclin-Dependent Kinase Inhibitor p21; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D016213:Cyclins / Q000235:genetics*; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000737:chemistry / Q000302:isolation & purification; D005091:Exons; D016368:Frameshift Mutation; D016161:Genes, Retinoblastoma; D016259:Genes, myc; D011905:Genes, ras; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008869:Microtubule-Associated Proteins / Q000235:genetics*; D009154:Mutation; D010190:Pancreatic Neoplasms / Q000235:genetics; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins
C493956:CDKN1A protein, human; C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D017931:DNA Primers; D004273:DNA, Neoplasm; D008869:Microtubule-Associated Proteins; D025521:Tumor Suppressor Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27; D018844:Cyclin-Dependent Kinases