The Fanconi anemia complementation group C gene (FAC) suppresses transformation of mutant fibroblasts by the SV40 virus.
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 FAC-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.
Liu
J M
JM
Hematology Branch, NHLBI, NIH, Bethesda, Maryland, USA.
Poiley
J
J
Devetten
M
M
Kajigaya
S
S
Walsh
C E
CE
D001483:Base Sequence; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D017931:DNA Primers; D018076:DNA, Complementary; D000229:Dependovirus; D005199:Fanconi Anemia / Q000235:genetics*; D005347:Fibroblasts; D005816:Genetic Complementation Test; D005822:Genetic Vectors; D006801:Humans; D019868:Kanamycin Kinase; D008969:Molecular Sequence Data; D009154:Mutation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D011994:Recombinant Proteins / Q000096:biosynthesis; D011995:Recombination, Genetic; D013539:Simian virus 40
D017931:DNA Primers; D018076:DNA, Complementary; D011994:Recombinant Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); D019868:Kanamycin Kinase