Depletion of c-myc with specific antisense sequences reverses the transformed phenotype in ras oncogene-transformed NIH 3T3 cells.
ras oncogene-transformed NIH 3T3 cells expressing glucocorticoid-inducible antisense c-myc cDNA transcripts at levels sufficient to deplete c-myc protein lost their transformed morphology and the ability to grow in soft agar; their ability to form tumors in nude mice was also impaired. These changes were dependent on the continuous expression of the antisense sequences. No major effects on plating efficiencies, growth rates in monolayer culture, or immortalization were observed in the revertant cells, indicating that the observed effects were not a toxic consequence of c-myc protein depletion. Transfection with the same vector expressing c-myc in the sense orientation or other control vectors had no effect on transformation. These results suggest that a certain minimum level of expression of c-myc is required for the maintenance of ras transformation in NIH 3T3 cells.
Sklar
M D
MD
Department of Radiation Oncology, University of Michigan School of Medicine, Ann Arbor 48109.
Thompson
E
E
Welsh
M J
MJ
Liebert
M
M
Harney
J
J
Grossman
H B
HB
Smith
M
M
Prochownik
E V
EV
D000818:Animals; D015139:Blotting, Southern; D002453:Cell Cycle; D002455:Cell Division; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002872:Chromosome Deletion; D016373:DNA, Antisense / Q000235:genetics*; D016259:Genes, myc; D011905:Genes, ras; D005822:Genetic Vectors; D007700:Kinetics; D051379:Mice; D010641:Phenotype; D010957:Plasmids; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis / Q000235:genetics; D014162:Transfection
D016373:DNA, Antisense; D016271:Proto-Oncogene Proteins c-myc