Reduced expression of p27 is a novel mechanism of docetaxel resistance in breast cancer cells

Breast Cancer Research

Andrew C Schofield²  Steven D Heys¹  Andrew W Hutcheon³  Susan E Moir¹  Sarah L McDonald¹  Kawan Shalli¹  Iain Brown¹ 

[1] Department of Surgery, University of Aberdeen, Medical School, Aberdeen, UK;Department of Molecular and Cell Biology, University of Aberdeen, Medical School, Aberdeen, UK;Department of Medical Oncology, Grampian University Hospitals NHS Trust, Aberdeen Royal Infirmary, Aberdeen, UK

关键词: p27;    gene expression;    drug resistance;    docetaxel;    breast cancer;   

Others  :  1118721
DOI  :  10.1186/bcr918

 received in 2004-03-10, accepted in 2004-07-06,  发布年份 2004

【 摘 要 】

Introduction

Docetaxel is one of the most effective chemotherapeutic agents in the treatment of breast cancer. Breast cancers can have an inherent or acquired resistance to docetaxel but the causes of this resistance remain unclear. However, apoptosis and cell cycle regulation are key mechanisms by which most chemotherapeutic agents exert their cytotoxic effects.

Methods

We created two docetaxel-resistant human breast cancer cell lines (MCF-7 and MDA-MB-231) and performed cDNA microarray analysis to identify candidate genes associated with docetaxel resistance. Gene expression changes were validated at the RNA and protein levels by reverse transcription PCR and western analysis, respectively.

Results

Gene expression cDNA microarray analysis demonstrated reduced p27 expression in docetaxel-resistant breast cancer cells. Although p27 mRNA expression was found to be reduced only in MCF-7 docetaxel-resistant sublines (2.47-fold), reduced expression of p27 protein was noted in both MCF-7 and MDA-MB-231 docetaxel-resistant breast cancer cells (2.83-fold and 3.80-fold, respectively).

Conclusions

This study demonstrates that reduced expression of p27 is associated with acquired resistance to docetaxel in breast cancer cells. An understanding of the genes that are involved in resistance to chemotherapy may allow further development in modulating drug resistance, and may permit selection of those patients who are most likely to benefit from such therapies.

【 授权许可】

   
2004 Brown et al.; licensee BioMed Central Ltd. This is an Open Access article: verbatim copying and redistribution of this article are permitted in all media for any purpose, provided this notice is preserved along with the article's original URL.

【 图 表 】

Figure 1.

Figure 2.

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