Loss of the putative tumor suppressor band 4.1B/Dal1 gene is dispensable for normal development and does not predispose to cancer

Mol Cell Biol. 2005 Nov;25(22):10052-9. doi: 10.1128/MCB.25.22.10052-10059.2005.

Abstract

The band 4.1 proteins are cytoskeletal proteins, harboring a conserved FERM domain highly homologous to the N-terminal FERM domain of ezrin, radixin, moesin, and merlin. Recently, a truncated form of the 4.1B protein, termed Dal-1, was identified in a screen as down regulated in adenocarcinoma of the lung and was mapped to chromosome 18p11.3, which is lost in 38% of primary non-small cell lung carcinoma tumors. Analysis of several meningiomas has shown that Dal-1 expression was lost in 76% of the tumors. To further elucidate the function of the 4.1B/Dal-1 gene in development and tumorigenesis we generated mice deficient for this allele. The 4.1B/Dal-1 null mice develop normally and are fertile. Rates of cellular proliferation and apoptosis in brain, mammary, and lung tissues from the 4.1B/Dal-1 null mice were indistinguishable from those seen with wild-type mice. Aging studies indicate that these mice do not have a propensity to develop tumors. Analysis of fibroblasts from these mice demonstrated that the growth characteristics and kinetics of these cells were not different from those of cells from the wild-type mice. These findings indicate that the 4.1B gene is not required for normal development and that 4.1B/Dal-1 does not function as a tumor suppressor gene.

Publication types

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

MeSH terms

  • Alleles
  • Animals
  • Apoptosis
  • Blotting, Southern
  • Blotting, Western
  • Brain / metabolism
  • Cell Death
  • Cell Proliferation
  • Cells, Cultured
  • Cloning, Molecular
  • Cytoskeletal Proteins / genetics*
  • Cytoskeletal Proteins / physiology*
  • DNA Primers / chemistry
  • Female
  • Genetic Predisposition to Disease*
  • Genotype
  • Immunohistochemistry
  • Kinetics
  • Lung / metabolism
  • Mammary Glands, Animal / metabolism
  • Membrane Proteins / genetics*
  • Membrane Proteins / physiology*
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Models, Genetic
  • Mutation
  • Neoplasms / genetics*
  • Neoplasms / metabolism
  • Neoplasms / pathology*
  • Polymerase Chain Reaction

Substances

  • Cytoskeletal Proteins
  • DNA Primers
  • Membrane Proteins
  • erythrocyte membrane band 4.1 protein