Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death
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Breast cancer cells with acquired antiestrogen resistance are sensitized to cisplatin-induced cell death. / Yde, Christina Westmose; Gyrd-Hansen, Mads; Lykkesfeldt, Anne E; Issinger, Olaf-Georg; Stenvang, Jan.
In: Molecular Cancer Therapeutics, Vol. 6, No. 6, 06.2007, p. 1869-1876.Research output: Contribution to journal › Journal article › Research › peer-review
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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
VL - 6
SP - 1869
EP - 1876
JO - Molecular Cancer Therapeutics
JF - Molecular Cancer Therapeutics
SN - 1535-7163
IS - 6
ER -
ID: 4043846