This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Middelburg, R. Articles by Lankelma, J. Search for Related Content PubMed PubMed Citation Articles by Middelburg, R. Articles by Lankelma, J.

Induction of p53 Up-Regulated Modulator of Apoptosis Messenger RNA by Chemotherapeutic Treatment of Locally Advanced Breast Cancer

¹ Department of Medical Oncology, VU University Medical Center; ² Central Microarray Facility, The Netherlands Cancer Institute; ³ VUmc Cancer Center Amsterdam, Amsterdam, the Netherlands; and ⁴ Instituto Nacional de Cancerología, Mexico City, Mexico

Requests for reprints: Jan Lankelma, Department of Medical Oncology, Room BR232, VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. Phone: 31-20-444-2603; Fax: 31-20-444-3844; E-mail: j.lankelma{at}vumc.nl.

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.

Key Words: BBC3 • PUMA • microarray • in vivo drug response • doxorubicin

This article has been cited by other articles:

				M. Lacroix, R.-A. Toillon, and G. Leclercq p53 and breast cancer, an update. Endocr. Relat. Cancer, June 1, 2006; 13(2): 293 - 325. [Abstract] [Full Text] [PDF]