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

Int J Cancer. 1998 May 29;76(5):720-8. doi: 10.1002/(sici)1097-0215(19980529)76:5<720::aid-ijc18>;2-7.


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.

MeSH terms

  • Alternative Splicing
  • Cell Cycle / physiology
  • Cell Cycle Proteins / biosynthesis*
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / physiology*
  • Cell Division / drug effects
  • Cell Division / physiology
  • Down-Regulation / drug effects
  • HeLa Cells / cytology
  • HeLa Cells / drug effects
  • Humans
  • Isomerism
  • Oligonucleotides, Antisense / pharmacology*
  • Phosphoprotein Phosphatases / biosynthesis*
  • Phosphoprotein Phosphatases / genetics
  • Phosphoprotein Phosphatases / physiology*
  • RNA, Messenger / metabolism
  • S Phase / drug effects*
  • S Phase / physiology
  • Sensitivity and Specificity
  • Thionucleotides / pharmacology*
  • cdc25 Phosphatases*


  • Cell Cycle Proteins
  • Oligonucleotides, Antisense
  • RNA, Messenger
  • Thionucleotides
  • Phosphoprotein Phosphatases
  • CDC25B protein, human
  • cdc25 Phosphatases