Induction of p53 up-regulated modulator of apoptosis messenger RNA by chemotherapeutic treatment of locally advanced breast cancer

Rutger Middelburg, Richard R. De Haas, Henk Dekker, Ron M. Kerkhoven, Paula R. Pohlmann, Adolfo Fuentes-Alburo, Alejandro Mohar, Herbert M. Pinedo, Jan Lankelma

Research output: Contribution to journalArticle

Abstract

Purpose: In biopsies of patients with locally advanced breast cancer, we investigated the in vivo changes of the gene expression pattern induced by chemotherapy to find genes that are potentially responsible for the efficacy of the drug. Experimental Design: Early cellular responses to chemotherapy-induced damage, both in vivo and in vitro, were investigated by analyzing chemotherapy-induced changes in gene expression profiles. Core biopsies were taken from nine patients with locally advanced breast cancer, before and at 6 hours after initiation of doxorubicin-based chemotherapy. Both samples were cohybridized on the same microarray containing 18,000 cDNA spots. Results: The analysis revealed marked differences in gene expression profile between treated and untreated samples. The gene which was most frequently found to be differentially expressed was p53 up-regulated modulator of apoptosis (PUMA). This gene was up-regulated in eight of nine patients with an average factor of 1.80 (range, 1.36-2.73). In vitro MCF-7 breast cancer cells exposed to clinically achievable doxorubicin concentrations for 6 hours revealed marked induction of PUMA mRNA, as well. Conclusions: This is the first report describing PUMA mRNA to be up-regulated as a response to chemotherapy in patients. Because PUMA is a known member of the family of BH3-only proapoptotic proteins, this finding suggests PUMA's potential importance for the response to anticancer drugs.

Original languageEnglish (US)
Pages (from-to)1863-1869
Number of pages7
JournalClinical Cancer Research
Volume11
Issue number5
DOIs
StatePublished - Mar 1 2005
Externally publishedYes

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Middelburg, R., De Haas, R. R., Dekker, H., Kerkhoven, R. M., Pohlmann, P. R., Fuentes-Alburo, A., Mohar, A., Pinedo, H. M., & Lankelma, J. (2005). Induction of p53 up-regulated modulator of apoptosis messenger RNA by chemotherapeutic treatment of locally advanced breast cancer. Clinical Cancer Research, 11(5), 1863-1869. https://doi.org/10.1158/1078-0432.CCR-04-1372