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

被引:66
作者
Brown, I [1 ]
Shalli, K
McDonald, SL
Moir, SE
Hutcheon, AW
Heys, SD
Schofield, AC
机构
[1] Univ Aberdeen, Sch Med, Dept Surg, Aberdeen AB9 2ZD, Scotland
[2] Aberdeen Royal Infirm, Grampian Univ Hosp NHS Trust, Dept Med Oncol, Aberdeen, Scotland
[3] Univ Aberdeen, Sch Med, Dept Mol & Cell Biol, Aberdeen AB9 2ZD, Scotland
关键词
breast cancer; docetaxel; drug resistance; gene expression; p27;
D O I
10.1186/bcr918
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
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.
引用
收藏
页码:R601 / R607
页数:7
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