Mutually Exclusive Inactivation of DMP1 and ARF/p53 in Lung Cancer
Copyright policy )Mutually Exclusive Inactivation of DMP1 and ARF/p53 in Lung Cancer
Dmp1 (Dmtf1) is activated by oncogenic Ras-Raf signaling and induces cell-cycle arrest in an Arf, p53-dependent fashion. The survival of K-ras(LA) mice was shortened by approximately 15 weeks in both Dmp1(+/-) and Dmp1(-/-) backgrounds, the lung tumors of which showed significantly decreased frequency of p53 mutations compared to Dmp1(+/+). Approximately 40% of K-ras(LA) lung tumors from Dmp1(+/+) mice lost one allele of the Dmp1 gene, suggesting the primary involvement of Dmp1 in K-ras-induced tumorigenesis. Loss of heterozygosity (LOH) of the hDMP1 gene was detectable in approximately 35% of human lung carcinomas, which was found in mutually exclusive fashion with LOH of INK4a/ARF or that of P53. Thus, DMP1 is a pivotal tumor suppressor for both human and murine lung cancers.
- University of British Columbia Canada
- Department of Pathology Taiwan
- Wake Forest University United States
- University of British Colombia Canada
Cancer Research, Lung Neoplasms, Loss of Heterozygosity, Mice, Transgenic, CELLCYCLE, Adenocarcinoma, Carcinoma, Adenosquamous, Mice, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Animals, Humans, Promoter Regions, Genetic, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation, Mice, Knockout, Cell Biology, Neoplasms, Experimental, DNA Methylation, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Oncology, Carcinoma, Squamous Cell, Signal Transduction
Cancer Research, Lung Neoplasms, Loss of Heterozygosity, Mice, Transgenic, CELLCYCLE, Adenocarcinoma, Carcinoma, Adenosquamous, Mice, Carcinoma, Non-Small-Cell Lung, Cell Line, Tumor, Animals, Humans, Promoter Regions, Genetic, Cyclin-Dependent Kinase Inhibitor p16, Cell Proliferation, Mice, Knockout, Cell Biology, Neoplasms, Experimental, DNA Methylation, Gene Expression Regulation, Neoplastic, Mice, Inbred C57BL, Oncology, Carcinoma, Squamous Cell, Signal Transduction
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