Role of DMP1 and its future in lung cancer diagnostics

Expert Rev Mol Diagn. 2008 Jul;8(4):435-47. doi: 10.1586/14737159.8.4.435.

Abstract

Lung cancer is the most lethal carcinoma worldwide. Mutations of p53, inactivation of p16(INK4a), and overexpression of cyclins E, A and B are independently associated with poor prognoses of patients, while the prognostic value of cyclin D1 or RB expression is inconclusive. Cyclin D binding myb-like protein 1 (Dmp1) encodes a DNA binding protein that receives signals from oncogenic Ras and functions as a tumor suppressor by activating the Arf-p53 [corrected] pathway. Dmp1 has been shown to be haplo-insufficient for tumor suppression in mouse models including K-ras-mediated lung carcinogenesis. The human DMP1 gene is located on chromosome 7q21, and our recent results revealed that the hDMP1 gene is deleted, but not mutated or silenced, in approximately 40 % of human non-small-cell lung carcinomas. These cases typically retained wild-type ARF and p53 and expressed very low levels of the hDMP1 protein. Thus, hDMP1 loss could be a novel diagnostic marker for non-small-cell lung carcinomas.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biomarkers, Tumor / biosynthesis
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Non-Small-Cell Lung / diagnosis
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Chromosomes, Human, Pair 7 / genetics
  • Chromosomes, Human, Pair 7 / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Cyclins / genetics
  • Cyclins / metabolism
  • Disease Models, Animal
  • Gene Deletion*
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Mice
  • Prognosis
  • Proto-Oncogene Proteins p21(ras) / genetics
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Transcription Factors / biosynthesis
  • Transcription Factors / genetics*
  • Tumor Suppressor Protein p53 / biosynthesis
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Biomarkers, Tumor
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclins
  • DMTF1 protein, human
  • Dmtf1 protein, mouse
  • TP53 protein, human
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins p21(ras)