The Fanconi anemia complementation group C gene (FAC) suppresses transformation of mutant fibroblasts by the SV40 virus

J. M. Liu, J. Poiley, M. Devetten, S. Kajigaya, C. E. Walsh

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Abstract

Fanconi anemia (FA) is a heterogeneous genetic syndrome manifested by bone marrow failure and consisting of at least five complementation groups (A, B, C, D, E). Mutations in a gene termed FAC are responsible for the C complementation group, but the function of the FAC protein remains obscure. FA patients are also highly cancer-prone; the molecular basis for this susceptibility is unclear but has led to the hypothesis that the wild-type FA gene may act as a tumor suppressor. In vitro, mutant FA primary fibroblasts are 3- to 50-fold more sensitive than normal fibroblasts to transformation in culture by the SV40 virus. We confirmed this marked susceptibility to transformation of a FAG-mutant primary fibroblast cell line, GM449. We then introduced a copy of the wild-type FAC cDNA into GM449 cells using a recombinant adeno-associated virus (rAAV) vector. We found that GM449 cells transduced with a copy of the normal FAC cDNA by a FAC-rAAV vector were at least 10-fold less prone to form transformed foci. Diminished transformation potential of transduced cells was a specific effect of the FAC cDNA since GM449 cells transduced with a rAAV vector not containing FAC retained marked susceptibility to SV40 transformation.

Original languageEnglish (US)
Pages (from-to)685-690
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume223
Issue number3
DOIs
Publication statusPublished - Jun 25 1996

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ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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