Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death.
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.
Yde
Christina Westmose
CW
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark.
Gyrd-Hansen
Mads
M
Lykkesfeldt
Anne E
AE
Issinger
Olaf-Georg
OG
Stenvang
Jan
J
D000970:Antineoplastic Agents / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000473:pathology*; D020169:Caspases / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D020847:Estrogen Receptor Modulators / Q000494:pharmacology*; D006801:Humans; D010447:Peptide Hydrolases / Q000378:metabolism
D000970:Antineoplastic Agents; D020847:Estrogen Receptor Modulators; D010447:Peptide Hydrolases; D020169:Caspases; D002945:Cisplatin