Author/Authors :
Ali Mallakin، نويسنده , , Ali and Sugiyama، نويسنده , , Takayuki and Taneja، نويسنده , , Pankaj and Matise، نويسنده , , Lauren A. and Frazier، نويسنده , , Donna P. and Choudhary، نويسنده , , Mayur and Hawkins، نويسنده , , Gregory A. and DʹAgostino Jr.، نويسنده , , Ralph B. and Willingham، نويسنده , , Mark C. and Inoue، نويسنده , , Kazushi، نويسنده ,
Abstract :
Summary
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.
