Loss of the putative tumor suppressor band 4.1B/Dal1 gene is dispensable for normal development and does not predispose to cancer.
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.
Yi
Chunling
C
Molecular and Cellular Oncogenesis Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
McCarty
Joseph H
JH
Troutman
Scott A
SA
Eckman
Matthew S
MS
Bronson
Roderick T
RT
Kissil
Joseph L
JL
D000483:Alleles; D000818:Animals; D017209:Apoptosis; D015139:Blotting, Southern; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016923:Cell Death; D049109:Cell Proliferation; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003598:Cytoskeletal Proteins / Q000235:genetics* / Q000502:physiology*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D007150:Immunohistochemistry; D007700:Kinetics; D008168:Lung / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008957:Models, Genetic; D009154:Mutation; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D016133:Polymerase Chain Reaction
D003598:Cytoskeletal Proteins; D017931:DNA Primers; D008565:Membrane Proteins; C028841:erythrocyte membrane band 4.1 protein