Deregulation of c-abl mediated cell growth after retroviral transfer and expression of antisense sequences.
To determine the role of c-abl during cell growth, we constructed a retrovirus vector alpha A, capable of expressing an antisense RNA directed against the abl mRNA. Based on v-abl-mediated 3T3 transformation assay, we showed that the number of transformed foci was reduced 50-94% when alpha A-infected 3T3 cells were superinfected with A-MuLV. Up to a 100% of inhibition could be observed when the time of infection was lengthened. Introduction of the antisense sequence into NIH3T3 cells resulted in reduction of growth rate. These cells entered into S phase from G1 phase of the cell cycle earlier in time than untransduced cells. Thus c-abl serves as a checkpoint during G1/S transition in the cell cycle, and its reduction resulted in deregulation of cell growth.
Daniel
R
R
Fels Institute for Cancer Research and Molecular Biology, Department of Biochemistry, Temple University, Philadelphia, Pennsylvania 19140, USA.
Cai
Y
Y
Wong
P M
PM
Chung
S W
SW
D016475:3T3 Cells; D000818:Animals; D001483:Base Sequence; D002453:Cell Cycle; D002455:Cell Division; D004247:DNA / Q000378:metabolism; D018014:Gene Transfer Techniques; D051379:Mice; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D016315:Proto-Oncogene Proteins c-abl / Q000037:antagonists & inhibitors / Q000502:physiology*; D016372:RNA, Antisense / Q000502:physiology*; D012190:Retroviridae / Q000235:genetics
D016372:RNA, Antisense; D004247:DNA; D016315:Proto-Oncogene Proteins c-abl