Induction of apoptosis by a dominant negative H-RAS mutant (116Y) in K562 cells.
Recent extensive work on apoptosis has begun to reveal its molecular mechanisms. Several genes that regulate apoptosis have been identified. Among them, the BCL2 gene is considered to be an important gene that inhibits apoptosis. However, there must be other genes, yet to be identified, which suppress apoptosis. It has been suggested that the activation of RAS function by BCR-ABL fusion protein in chronic myelogenous leukemia may be an important mechanism in the BCR-ABL mediated transformation. Therefore, in this study we have investigated whether the suppression of endogenous H-RAS function inhibits the BCR-ABL mediated transforming activity in a K562 human chronic myelogenous leukemia cell line. The induced expression of a dominant negative v-H-RAS mutant (116Y) in K562 cells has resulted in cell death. The morphological characteristics and the detection of fragmented DNA by gel electrophoresis in the dead cells have revealed that this cell death is apoptosis. These results directly indicate that the RAS gene as well as the BCL2 gene has an ability to suppress apoptosis.
Laboratory of Molecular Genetics, Hokkaido University School of Medicine, Japan.
N
N
Sakai
Y
Y
Ogiso
H
H
Fujita
H
H
Watari
T
T
Koike
N
N
Kuzumaki
D017209:Apoptosis / Q000235:genetics*; D001483:Base Sequence; D002460:Cell Line; D002470:Cell Survival; D004249:DNA Damage; D017931:DNA Primers; D004273:DNA, Neoplasm / Q000302:isolation & purification; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism; D015870:Gene Expression; D011905:Genes, ras; D006801:Humans; D007700:Kinetics; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D013997:Time Factors; D014162:Transfection; D014407:Tumor Cells, Cultured; D001616:beta-Galactosidase / Q000096:biosynthesis
D017931:DNA Primers; D004273:DNA, Neoplasm; D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D016044:Fusion Proteins, bcr-abl; D001616:beta-Galactosidase