Inhibition of the proliferative effect of transforming growth factor-alpha by c-myc antisense DNA in human ovarian cancer cells.
In search of critical genes associated with the mechanism of transforming growth factor-alpha (TGF alpha) action in human ovarian cancer, it was found that TGF alpha stimulates c-myc gene expression in human ovarian NIH:OVCAR-3. The role of c-myc in TGF alpha-stimulated growth of NIH:OVCAR-3 cells was examined by the use of the synthetic antisense-myc phosphorothioate oligonucleotide (OPT). Prior exposure of NIH:OVCAR-3 cells to an antisense-myc OPT inhibited TGF alpha-stimulated cell growth and DNA synthesis in a dose-dependent and sequence-specific manner over 4 days. c-Myc protein expression was down-regulated in the antisense-myc treated cells. These results demonstrate both the specific and durable effects of the antisense-myc OPT. Furthermore, the results suggest a role for c-myc in TGF alpha-stimulated cell proliferation.
Park
H Y
HY
Department of Biochemistry, Ewha Medical Research Center, College of Medicine, Ewha Womans University, Seoul, Korea.
D002455:Cell Division / Q000187:drug effects / Q000235:genetics; D004247:DNA / Q000096:biosynthesis / Q000187:drug effects; D004261:DNA Replication / Q000187:drug effects; D016373:DNA, Antisense / Q000502:physiology*; D004273:DNA, Neoplasm / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D016259:Genes, myc / Q000502:physiology*; D006131:Growth Inhibitors / Q000494:pharmacology*; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000235:genetics / Q000473:pathology*; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology; D016211:Transforming Growth Factor alpha / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D016373:DNA, Antisense; D004273:DNA, Neoplasm; D006131:Growth Inhibitors; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D013873:Thionucleotides; D016211:Transforming Growth Factor alpha; D004247:DNA