Induction of cell death in antiestrogen resistant human breast cancer cells by the protein kinase CK2 inhibitor DMAT.
Protein kinase CK2 is involved in cell proliferation and survival, and found overexpressed in virtually all types of human cancer, including breast cancer. We demonstrate that inhibition of CK2 with 2-dimethylamino-4,5,6,7-tetrabromo-benzimidazole (DMAT), a potent and specific CK2 inhibitor, results in caspase-mediated killing of human breast cancer cells with acquired resistance to antiestrogens, while DMAT fails to kill parental MCF-7 cells. The antiestrogen resistant breast cancer cells express reduced levels of Bcl-2 compared to MCF-7 cells. Reduced Bcl-2 protein level is also found in a tamoxifen resistant human breast tumor grown as a xenograft. We show that re-expression of Bcl-2 partially rescues antiestrogen resistant MCF-7 sublines from DMAT-induced cell death. In summary, our data suggest a novel role of CK2 in antiestrogen resistance.
Yde
Christina Westmose
CW
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark.
Frogne
Thomas
T
Lykkesfeldt
Anne E
AE
Fichtner
Iduna
I
Issinger
Olaf-Georg
OG
Stenvang
Jan
J
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D001562:Benzimidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D047390:Casein Kinase II / Q000037:antagonists & inhibitors* / Q000378:metabolism; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D020847:Estrogen Receptor Modulators / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D000077267:Fulvestrant; D006801:Humans; D053284:Polyunsaturated Alkamides / Q000494:pharmacology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology; D013997:Time Factors; D014162:Transfection
C492322:2-dimethylamino-4,5,6,7-tetrabromo-1H-benzimidazole; D000970:Antineoplastic Agents; D001562:Benzimidazoles; D020847:Estrogen Receptor Modulators; D053284:Polyunsaturated Alkamides; D019253:Proto-Oncogene Proteins c-bcl-2; D013629:Tamoxifen; D000077267:Fulvestrant; D004958:Estradiol; C051781:ICI 164384; D047390:Casein Kinase II; D020169:Caspases