Inhibition of the proliferative effect of transforming growth factor-α by c-myc antisense DNA in human ovarian cancer cells

Abstract

In search of critical genes associated with the mechanism of transforming growth factor-α. (TGFα) action in human ovarian cancer, it was found that TGFα stimulates c-myc gene expression in human ovarian NIH:OVCAR-3. The role of c-myc in TGFα-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 TGFα-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 TGFα-stimulated cell proliferation.