Pol ι Is a Candidate for the Mouse Pulmonary Adenoma Resistance 2 Locus, a Major Modifier of Chemically Induced Lung Neoplasia
| Autor: | Theodora R. Devereux, Scott D. McCulloch, Ming You, Min Wang, Thomas A. Kunkel, Colleen H. Anna, Yian Wang, Haris G. Vikis, Wanda Holliday, Kun-Liang Guan, Katarzyna Bebenek |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Adenoma
Cancer Research Candidate gene Lung Neoplasms Mice Inbred A DNA polymerase Molecular Sequence Data Single-nucleotide polymorphism DNA-Directed DNA Polymerase medicine.disease_cause Polymorphism Single Nucleotide Proto-Oncogene Proteins p21(ras) Mice Proto-Oncogene Proteins Gene expression Tumor Cells Cultured medicine Animals Humans Amino Acid Sequence RNA Messenger Lung Gene Regulation of gene expression Mice Inbred BALB C Sequence Homology Amino Acid biology Molecular biology Immunity Innate Gene Expression Regulation Neoplastic Alternative Splicing Oncology DNA Polymerase iota ras Proteins biology.protein Carcinogenesis DNA Polymerase Iota |
| Zdroj: | Cancer Research. 64:1924-1931 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | In this study, we performed systematic candidate gene analyses of the Pulmonary adenoma resistance 2 locus. Differential gene expression in lung tissues and nucleotide polymorphisms in coding regions between A/J and BALB/cJ mice were examined using reverse transcription-PCR and direct sequencing. Although not all genes in the interval were analyzed at this moment due to the recent database updating, we have found that the Pol ι gene, encoding the DNA polymerase ι, contains 25 nucleotide polymorphisms in its coding region between A/J and BALB/cJ mice, resulting in a total of ten amino acid changes. Primer extension assays with purified BALB/cJ and A/J proteins in vitro demonstrate that both forms of Pol ι are active but that they may differ in substrate discrimination, which may affect the formation of Kras2 mutations in mouse lung tumors. Altered expression of POL ι protein and an amino acid-changing nucleotide polymorphism were observed in human lung cancer cells, suggesting a possible role in the development of lung cancer. Thus, our data support the Pol ι gene as a modifier of lung tumorigenesis by altering DNA polymerase activity. |
| Databáze: | OpenAIRE |
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