[HTML][HTML] Mutually exclusive inactivation of DMP1 and ARF/p53 in lung cancer

A Mallakin, T Sugiyama, P Taneja, LA Matise… - Cancer cell, 2007 - cell.com
A Mallakin, T Sugiyama, P Taneja, LA Matise, DP Frazier, M Choudhary, GA Hawkins…
Cancer cell, 2007cell.com
Summary 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∼
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 …
Summary
Dmp1 (Dmtf1) is activated by oncogenic Ras-Raf signaling and induces cell-cycle arrest in an Arf, p53-dependent fashion. The survival of K-rasLA mice was shortened by ∼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-rasLA 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 ∼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.
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