Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53

Oncogene. 2007 Feb 15;26(7):1003-12. doi: 10.1038/sj.onc.1209864. Epub 2006 Aug 14.


Cancers harboring dominant-negative p53 mutations are often aggressive and difficult to treat. Direct attempts to restore wild-type p53 function have produced little clinical benefit. We investigated whether targeting a p53-target gene could induce certain tumor-suppressor characteristics. We found that inhibition of stathmin, a microtubule regulator that can be transcriptionally repressed by wild-type p53, restored certain wild-type functions to cancer cells with mutant p53. Silencing of stathmin by small interfering RNA (siRNA) in mutant p53 cell lines lowered expression to that observed following activation of wild-type p53 by DNA damage in wild-type p53 cell lines. siRNA-induced repression of stathmin decreased cell proliferation, viability and clonogenicity in mutant p53 cell lines. Furthermore, knockdown of stathmin partially restored cell-cycle regulation and activation of apoptosis. Therefore, targeting stathmin, a gene product that is overexpressed in the presence of mutant p53, may represent a novel approach to treating cancers with aberrant p53 function.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis / genetics
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Survival / genetics
  • Female
  • Gene Silencing / physiology*
  • Gene Targeting / methods
  • Growth Inhibitors / biosynthesis*
  • Growth Inhibitors / genetics*
  • Growth Inhibitors / physiology
  • Humans
  • Mutation*
  • Stathmin / antagonists & inhibitors*
  • Stathmin / biosynthesis
  • Stathmin / genetics
  • Tumor Suppressor Protein p53 / biosynthesis*
  • Tumor Suppressor Protein p53 / genetics*
  • Tumor Suppressor Protein p53 / physiology


  • Growth Inhibitors
  • Stathmin
  • Tumor Suppressor Protein p53