Journal article
Estrogen receptor alpha mediates breast cancer cell resistance to paclitaxel through inhibition of apoptotic cell death
Cancer research (Chicago, Ill.), Vol.67(11), pp.5337-5344
06/01/2007
DOI: 10.1158/0008-5472.CAN-06-4582
PMID: 17545614
Abstract
Estrogen receptors (ER) are expressed in similar to 65% of human breast cancer. Cumulative data from clinical trials and retrospective analyses suggest that some chemotherapeutic agents may be less effective in patients with ER-positive (ER+) tumors than those with ER-negative (ER-) tumors. Paclitaxel is an active agent used in breast cancer chemotherapy. To investigate the possible influence of ER on the therapeutic efficacy of paclitaxel and its underlying mechanism, we established several isogenic ER+ cell lines by stable transfection of ER alpha expression vectors into ER- breast cancer BCap37 cells. We showed that 17-beta estradiol significantly reduces the overall cytotoxicity of paclitaxel in BCap37-expressing ER alpha but has no influence on the ER- parental cells. Further analyses indicate that expression of ER alpha in BCap37 cells mainly interferes with paclitaxel-induced apoptotic cell death, without affecting paclitaxel-induced microtubule bundling and mitotic arrest. Moreover, we found that the addition of ICI 182,780 (Fulvestrant), a selective ER down-regulator, could completely reverse the resistance of ER+ BCap37 cells to paclitaxel. These findings showed that ER alpha-mediated breast tumor cell resistance to paclitaxel was through selective inhibition of paclitaxel-induced tumor cell apoptosis. Additionally, the combination of ICI 182,780 also sensitizes MCF-7 and T47D cell lines to the treatment of paclitaxel, which further confirmed the correlation between ER alpha, and drug resistance in ER+ tumor cells. The results obtained from this study provide useful information for understanding ER-mediated resistance to paclitaxel and possibly other antineoplastic agents.
Details
- Title: Subtitle
- Estrogen receptor alpha mediates breast cancer cell resistance to paclitaxel through inhibition of apoptotic cell death
- Creators
- Meihua Sui - Medical University of South CarolinaYi Huang - Johns Hopkins UniversityBen Ho Park - Johns Hopkins UniversityNancy E. DavidsonWeimin Fan - Medical University of South Carolina
- Resource Type
- Journal article
- Publication Details
- Cancer research (Chicago, Ill.), Vol.67(11), pp.5337-5344
- Publisher
- Amer Assoc Cancer Research
- DOI
- 10.1158/0008-5472.CAN-06-4582
- PMID
- 17545614
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Number of pages
- 8
- Grant note
- P50CA088843 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) CA109274; CA88843; CA92280 / NCI NIH HHS; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI)
- Language
- English
- Date published
- 06/01/2007
- Academic Unit
- Internal Medicine
- Record Identifier
- 9984383302802771
Metrics
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