Antisense phosphorothioate oligonucleotides specifically down‐regulate cdc25B causing S‐phase delay and persistent antiproliferative effects

Cell cycle progression in mammalian cells is regulated by a family of cyclin‐dependent kinases (cdks) that are activated by a family of 3 cdc25 phosphatases: cdc25A, cdc25B and cdc25C. We examined the expression of mRNA and protein of all 3 cdc25s during the HeLa cell cycle, and found that cdc25B protein has a unique and limited pattern of expression relative to other cdc25 homologs. Antisense oligonucleotides reduced cdc25B mRNA levels and dysregulated protein expression, while inhibiting S‐phase progression in synchronized HeLa cells. Scrambled control oligonucleotides had no effect. Antisense oligonucleotides transfected in early G2‐phase had no effect on cell cycle progression. A direct correlation between down‐regulation of cdc25B and inhibition of thymidine incorporation was found using several oligonucleotides. Our results suggest a role for cdc25B in S‐phase and demonstrate that inhibition of cdc25B has persistent antiproliferative effects. Int. J. Cancer 76:720–728, 1998.© 1998 Wiley‐Liss, Inc.