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

TY - JOUR

T1 - Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death

AU - Yde, Christina Westmose

AU - Gyrd-Hansen, Mads

AU - Lykkesfeldt, Anne E

AU - Issinger, Olaf-Georg

AU - Stenvang, Jan

PY - 2007/6

Y1 - 2007/6

N2 - 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.

AB - 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.

KW - Antineoplastic Agents

KW - Blotting, Western

KW - Breast Neoplasms

KW - Caspases

KW - Cell Death

KW - Cell Line, Tumor

KW - Cisplatin

KW - Estrogen Receptor Modulators

KW - Humans

KW - Peptide Hydrolases

U2 - 10.1158/1535-7163.MCT-07-0072

DO - 10.1158/1535-7163.MCT-07-0072

M3 - Journal article

C2 - 17575115

SN - 1535-7163

VL - 6

SP - 1869

EP - 1876

JO - Molecular Cancer Therapeutics

JF - Molecular Cancer Therapeutics

IS - 6

ER -