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Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer.

ABSTRACT: 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.

SUBMITTER: Mallakin A

PROVIDER: S-EPMC2239345 | biostudies-literature | 2007 Oct

REPOSITORIES: biostudies-literature

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Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer.

Mallakin Ali A Sugiyama Takayuki T Taneja Pankaj P Matise Lauren A LA Frazier Donna P DP Choudhary Mayur M Hawkins Gregory A GA D'Agostino Ralph B RB Willingham Mark C MC Inoue Kazushi K

Cancer cell 20071001 4

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 ...[more]

PMID: 17936562

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