Role of DMP1 and its future in lung cancer diagnostics

摘要

Lung cancer is the most lethal carcinoma worldwide. Mutations of p53, inactivation ofnp16INK4a, and overexpression of cyclins E, A and B are independently associated with poornprognoses of patients, while the prognostic value of cyclin D1 or RB expression isninconclusive. Cyclin D binding myb-like protein 1 (Dmp1) encodes a DNA binding proteinnthat receives signals from oncogenic Ras and functions as a tumor suppressor by activatingnthe Arf–p53 pathway. Dmp1 has been shown to be haplo-insufficient for tumor suppressionnin mouse models including K-ras-mediated lung carcinogenesis. The human DMP1 gene isnlocated on chromosome 7q21, and our recent results revealed that the hDMP1 gene isndeleted, but not mutated or silenced, in approximately 40 % of human non-small-cell lungncarcinomas. These cases typically retained wild-type ARF and p53 and expressed very lownlevels of the hDMP1 protein. Thus, hDMP1 loss could be a novel diagnostic marker fornnon-small-cell lung carcinomas.