Deletion ofXPCleads to lung tumors in mice and is associated with early events in human lung carcinogenesis
| Autor: | Susana Velasco-Miguel, R. Ilona Linnoila, Andrew D. Patterson, Albert J. Fornace, Robyn T. Philburn, M. Christine Hollander, Errol C. Friedberg |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Lung Neoplasms DNA repair Cell Cycle Proteins Biology medicine.disease_cause Metastasis Mice Carcinoma Non-Small-Cell Lung medicine Animals Humans Lung cancer Alleles Mice Knockout Mutation Multidisciplinary Lung Chromosome Mapping Nuclear Proteins Cancer Biological Sciences respiratory system medicine.disease respiratory tract diseases DNA-Binding Proteins medicine.anatomical_structure Chromosomes Human Pair 1 Immunology Cancer research Adenocarcinoma Female Chromosomes Human Pair 3 Carcinogenesis Gene Deletion DNA Damage |
| Zdroj: | Proceedings of the National Academy of Sciences. 102:13200-13205 |
| ISSN: | 1091-6490 0027-8424 |
| Popis: | Chromosome 3p and 1p deletions are among the most frequent genetic changes in human lung cancer and although candidate tumor suppressor genes have been identified in these regions, no causative correlations have been drawn between deletion or mutation of these and lung carcinogenesis. We identifyXPCandGadd45aas genes within each of these regions involved in lung tumor initiation and progression, respectively. One hundred percent ofXPC-/- mice develop multiple spontaneous lung tumors with a minority progressing to non-small cell lung adenocarcinoma, occasionally with metastasis to adjacent lymph nodes. Deletion ofGadd45aalone does not lead to increased lung tumors in mice, but coupled with anXPCdeletion, it results in lung tumor progression. Analysis of published data indicated allelic loss ofXPCin most human lung tumors and allelic loss ofGadd45ain some human lung and other cancer types. Because DNA repair capacity is compromised inXPC+/- cells, it is possible that the loss of a singleXPCallele in the human lung might confer a mutator phenotype. Coupled with cigarette carcinogens, decreased DNA repair would lead to additional mutations in genes such as p53 that are frequent targets in lung cancer. |
| Databáze: | OpenAIRE |
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