Yde Christina Westmose, Frogne Thomas, Lykkesfeldt Anne E, Fichtner Iduna, Issinger Olaf-Georg, Stenvang Jan
Department of Biochemistry and Molecular Biology, University of Southern Denmark, Campusvej 55, DK-5230 Odense, Denmark.
Cancer Lett. 2007 Oct 28;256(2):229-37. doi: 10.1016/j.canlet.2007.06.010. Epub 2007 Jul 16.
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.
蛋白激酶CK2参与细胞增殖与存活，且在包括乳腺癌在内的几乎所有类型的人类癌症中均呈过表达。我们证明，用强效特异性CK2抑制剂2-二甲基氨基-4,5,6,7-四溴苯并咪唑（DMAT）抑制CK2，可导致半胱天冬酶介导的对获得性抗雌激素耐药的人乳腺癌细胞的杀伤，而DMAT未能杀死亲本MCF-7细胞。与MCF-7细胞相比，抗雌激素耐药乳腺癌细胞中Bcl-2的表达水平降低。在作为异种移植生长的他莫昔芬耐药人乳腺肿瘤中也发现Bcl-2蛋白水平降低。我们表明，Bcl-2的重新表达部分挽救了抗雌激素耐药的MCF-7亚系免受DMAT诱导的细胞死亡。总之，我们的数据表明CK2在抗雌激素耐药中具有新作用。
