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

E. Alli, Jin-Ming Yang, W. N. Hait

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1003-1012
Number of pages10
JournalOncogene
Volume26
Issue number7
DOIs
StatePublished - Feb 15 2007

Fingerprint

Stathmin
Breast Neoplasms
Cell Line
Neoplasms
Small Interfering RNA
p53 Genes
Microtubules
DNA Damage
Cell Survival
Cell Cycle
Cell Proliferation
Apoptosis
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Alli, E. ; Yang, Jin-Ming ; Hait, W. N. / Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. In: Oncogene. 2007 ; Vol. 26, No. 7. pp. 1003-1012.
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Silencing of stathmin induces tumor-suppressor function in breast cancer cell lines harboring mutant p53. / Alli, E.; Yang, Jin-Ming; Hait, W. N.

In: Oncogene, Vol. 26, No. 7, 15.02.2007, p. 1003-1012.

Research output: Contribution to journalArticle

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AB - 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.

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