期刊
CANCERS
卷 11, 期 9, 页码 -出版社
MDPI
DOI: 10.3390/cancers11091285
关键词
breast cancer; ionizing radiation; intermediate conductance calcium-activated potassium channel; K(Ca)3.1; SK4; IK; KCNN4; mouse mammary tumor virus polyoma middle T antigen; MMTV-PyMT; TRAM-34
类别
资金
- Deutsche Forschungsgemeinschaft
- German Cancer Aid [70112872, 70113144]
- ICEPHA Graduate Program Membrane-associated Drug Targets in Personalized Cancer Medicine
- Studienstiftung des deutschen Volkes
K(Ca)3.1 K+ channels reportedly contribute to the proliferation of breast tumor cells and may serve pro-tumor functions in the microenvironment. The putative interaction of K(Ca)3.1 with major anti-cancer treatment strategies, which are based on cytotoxic drugs or radiotherapy, remains largely unexplored. We employed K(Ca)3.1-proficient and -deficient breast cancer cells derived from breast cancer-prone MMTV-PyMT mice, pharmacological K(Ca)3.1 inhibition, and a syngeneic orthotopic mouse model to study the relevance of functional K(Ca)3.1 for therapy response. The K(Ca)3.1 status of MMTV-PyMT cells did not determine tumor cell proliferation after treatment with different concentrations of docetaxel, doxorubicin, 5-fluorouracil, or cyclophosphamide. K(Ca)3.1 activation by ionizing radiation (IR) in breast tumor cells in vitro, however, enhanced radioresistance, probably via an involvement of the channel in IR-stimulated Ca2+ signals and DNA repair pathways. Consistently, K(Ca)3.1 knockout increased survival time of wildtype mice upon syngeneic orthotopic transplantation of MMTV-PyMT tumors followed by fractionated radiotherapy. Combined, our results imply that K(Ca)3.1 confers resistance to radio- but not to chemotherapy in the MMTV-PyMT breast cancer model. Since K(Ca)3.1 is druggable, K(Ca)3.1 targeting concomitant to radiotherapy seems to be a promising strategy to radiosensitize breast tumors.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据