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Research Articles: Therapeutics, Targets, and Development

Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

¹ Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark; ² Apoptosis Laboratory and ³ Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, Copenhagen, Denmark

Requests for reprints: Anne E. Lykkesfeldt, Department of Tumor Endocrinology, Institute of Cancer Biology, Danish Cancer Society, DK-2100 Copenhagen, Denmark. Phone: 45-352-57323; Fax: 45-352-57721. E-mail: al{at}cancer.dk

Abstract

Antiestrogens are currently used for treating breast cancer patients who have estrogen receptor–positive tumors. However, patients with advanced disease will eventually develop resistance to the drugs. Therefore, compounds effective on antiestrogen-resistant tumors will be of great importance for future breast cancer treatment. In this study, we have investigated the effect of the chemotherapeutic compound cisplatin using a panel of antiestrogen-resistant breast cancer cell lines established from the human breast cancer cell line MCF-7. We show that the antiestrogen-resistant cells are significantly more sensitive to cisplatin-induced cell death than antiestrogen-sensitive MCF-7 cells and we show that cisplatin induces cell death by activating both the caspase and lysosomal death pathways. The antiestrogen-resistant cell lines express lower levels of antiapoptotic Bcl-2 protein compared with parental MCF-7 cells. Our data show that Bcl-2 can protect antiestrogen-resistant breast cancer cells from cisplatin-induced cell death, indicating that the reduced expression of Bcl-2 in the antiestrogen-resistant cells plays a role in sensitizing the cells to cisplatin treatment. [Mol Cancer Ther 2007;6(6): 1869–76]

Grant support: Danish Cancer Society.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 1/31/07; revised 4/ 4/07; accepted 4/27/07.