Deletion and differential expression of p16INK4a in mouse lung tumors
| Autor: | S K Middleton, Steven A. Belinsky, D. S. Swafford, J. Tesfaigzi, C H Kennedy |
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| Rok vydání: | 1997 |
| Předmět: |
Cancer Research
Lung Neoplasms Tumor suppressor gene Mice Inbred A Cell Cycle Proteins Biology medicine.disease_cause Methylation Retinoblastoma Protein Loss of heterozygosity Mice Cyclin D1 Gene mapping Cyclins Gene expression Gene cluster medicine Animals Genes Tumor Suppressor RNA Messenger Cyclin-Dependent Kinase Inhibitor p16 Cyclin-Dependent Kinase Inhibitor p15 Oncogene Proteins Tumor Suppressor Proteins Chromosome Mapping General Medicine Gene Expression Regulation Neoplastic Chromosome 4 Mutation Cancer research Carrier Proteins Carcinogenesis Gene Deletion Transcription Factors |
| Zdroj: | Carcinogenesis. 18:115-120 |
| ISSN: | 1460-2180 |
| DOI: | 10.1093/carcin/18.1.115 |
| Popis: | Recent allelotyping of chemical-induced lung tumors in hybrid mice has detected loss of heterozygosity on chromosome 4 in a region involving the interferon-{alpha} (IFN-{alpha}) gene cluster that is syntenic to human chromosome 9p21-22, the location of the p16{sup INK4a}(p16) and (p15) tumor suppressor genes. The purpose of the current investigation was to characterize the expression of p16 and p15 in lung tumors and tumor-derived cell lines induced in Ad mice by exposure to the tobacco-specific nitrosamine, 4-methylnitrosamino-1-(3-pyridyl)-1-butanone (NNK). Expression of p16 and p15 was detected in all primary lung tumors; however, levels of expression of p16 differed by up to 15-fold between tumors. This is the first study to note a marked difference in the expression of the p16 gene in primary lung tumors. The apparent low levels of expression seen in approximately half of the tumors was not attributed to deletion, mutation or methylation of the p16 gene. Conversely, the high levels of p16 expression were not the result of effects on the retinoblastoma gene (Rb) or cyclin D1 proteins but most likely in response to a dysfunction elsewhere within this pathway. In contrast to the detection of p16 expression in primary tumors, this gene was deleted in allmore » four cell lines. Three of four cell lines also showed loss of the p15 gene. Mapping of these homozygous deletions on chromosome 4 revealed that the p16 gene resides near the D4MIT77 marker, which is located approximately 12 cM proximal to the IFN-{alpha} gene cluster, thereby implicating the p16 gene as one of the targets within the allelic deletions detected previously in primary lung tumors from hybrid mice.« less |
| Databáze: | OpenAIRE |
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