A panel of isogenic human cancer cells suggests a therapeutic approach for cancers with inactivated p53

Surojit Sur, Raymond Pagliarini, Fred Bunz, Carlo Rago, Luis A. Diaz, Kenneth W. Kinzler, Bert Vogelstein, Nickolas Papadopoulos

Research output: Contribution to journalArticle

Abstract

Through targeted homologous recombination, we developed a panel of matched colorectal cancer cell lines that differ only with respect to their endogenous TP53 status. We then used these lines to define the genes whose expression was altered after DNA damage induced by ionizing radiation. Transcriptome analyses revealed a consistent upregulation of polo-like kinase 1 (PLK1) as well as other genes controlling the G2/M transition in the cells whose TP53 genes were inactivated compared with those with WT TP53 genes. This led to the hypothesis that the viability of stressed cells without WT TP53 depended on PLK1. This hypothesis was validated by demonstrating that stressed cancer cells without WT TP53 alleles were highly sensitive to PLK1 inhibitors, both in vivo and in vitro.

Original languageEnglish (US)
Pages (from-to)3964-3969
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume106
Issue number10
DOIs
StatePublished - Mar 10 2009

ASJC Scopus subject areas

  • General

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