Inactivation of p53 signaling by p73 or PTEN ablation results in a transformed phenotype that remains susceptible to nutlin-3 mediated apoptosis

Rocky Cipriano, John T. Patton, Lindsey Mayo, Mark W. Jackson

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

The p53 signaling pathway is frequently disrupted in carcinogenesis. However, roughly 50% of all cancers express wild-type p53 and have alterations in accessory signaling components required for p53 activity. Using the well described E1A/RAS transformation model, in which p53 activity must be suppressed for transformation, we show here that p53 is inactive and unable to suppress transformation following ablation of p73 or PTEN. However, despite the transformed phenotype conferred by p53 inactivation following p73 or PTEN loss, p53 could be fully activated by Nutlin-3, resulting in efficient caspase-mediated apoptosis. Our novel and unexpected finding provides important information regarding the efficacy of Nutlin-3 and indicates that patients with tumors deficient in p53 function due to p73 or PTEN loss may benefit from Nutlin-3 treatment.

Original languageEnglish
Pages (from-to)1373-1379
Number of pages7
JournalCell Cycle
Volume9
Issue number7
StatePublished - Apr 1 2010

Fingerprint

Apoptosis
Phenotype
Caspases
Neoplasms
Carcinogenesis
nutlin 3
Therapeutics

Keywords

  • BCL-2
  • Nutlin-3
  • p53
  • p73
  • PTEN

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology
  • Developmental Biology

Cite this

Inactivation of p53 signaling by p73 or PTEN ablation results in a transformed phenotype that remains susceptible to nutlin-3 mediated apoptosis. / Cipriano, Rocky; Patton, John T.; Mayo, Lindsey; Jackson, Mark W.

In: Cell Cycle, Vol. 9, No. 7, 01.04.2010, p. 1373-1379.

Research output: Contribution to journalArticle

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