Louis Wc Chow1,2,3, Ka-Shun Cheng4,5, Kar-Lok Wong4, Yuk-Man Leung6. 1. State Key Laboratory of Quality Research in Chinese Medicines, Macau University of Science and Technology, Taipa, Macau 999078, China. 2. UNIMED Medical Institute, Hong Kong 999077, China. 3. Organisation for Oncology and Translational Research, Hong Kong 999077, China. 4. Department of Anesthesiology, China Medical University Hospital, Taichung 40447, Taiwan, China. 5. Department of Anesthesiology, the Qingdao University Yuhuangding Hospital, Yantai 264000, China. 6. Department of Physiology, China Medical University, Taichung 40402, Taiwan, China.
Abstract
OBJECTIVE: A variety of ion channels have been implicated in breast cancer proliferation and metastasis. Voltage-gated K+ (Kv) channels not only cause repolarization in excitable cells, but are also involved in multiple cellular functions in non-excitable cells. In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells. METHODS: Transwell technique was used to separate migratory cells from non-migratory ones and these two groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca2+. Cell migration was examined in the absence or presence of Kv channel blockers. RESULTS: When compared with non-migratory cells, migratory cells had much higher Kv current densities, but rather unexpectedly, more depolarized membrane potential and reduced Ca2+ influx. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the presence of Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv3.3, Kv3.4 and Kv4.3 channels. Cell migration was markedly inhibited by tetraethylammonium (TEA), a delayed rectifier Kv channel blocker, but not by 4-aminopyridine, an A-type Kv channel blocker. CONCLUSIONS: Taken together, our results show that increased Kv channel expression played a role in BT474 cell migration, and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis. The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Ca2+ influx.
OBJECTIVE: A variety of ion channels have been implicated in breast cancer proliferation and metastasis. Voltage-gated K+ (Kv) channels not only cause repolarization in excitable cells, but are also involved in multiple cellular functions in non-excitable cells. In this study we investigated the role of Kv channels in migration of BT474 breast cancer cells. METHODS: Transwell technique was used to separate migratory cells from non-migratory ones and these two groups of cells were subject to electrophysiological examinations and microfluorimetric measurements for cytosolic Ca2+. Cell migration was examined in the absence or presence of Kv channel blockers. RESULTS: When compared with non-migratory cells, migratory cells had much higher Kv current densities, but rather unexpectedly, more depolarized membrane potential and reduced Ca2+ influx. Reverse transcriptase-polymerase chain reaction (RT-PCR) analysis revealed the presence of Kv1.1, Kv1.3, Kv1.5, Kv2.1, Kv3.3, Kv3.4 and Kv4.3 channels. Cell migration was markedly inhibited by tetraethylammonium (TEA), a delayed rectifier Kv channel blocker, but not by 4-aminopyridine, an A-type Kv channel blocker. CONCLUSIONS: Taken together, our results show that increased Kv channel expression played a role in BT474 cell migration, and Kv channels could be considered as biomarkers or potential therapeutic targets for breast cancer metastasis. The mechanism(s) by which Kv channels enhanced migration appeared unrelated to membrane hyperpolarization and Ca2+ influx.
Entities:
Keywords:
Breast cancer; Kv channels; biomarkers; migration
Authors: Scott P Fraser; James K J Diss; Athina-Myrto Chioni; Maria E Mycielska; Huiyan Pan; Rezan F Yamaci; Filippo Pani; Zuzanna Siwy; Monika Krasowska; Zbigniew Grzywna; William J Brackenbury; Dimis Theodorou; Meral Koyutürk; Handan Kaya; Esra Battaloglu; Manuela Tamburo De Bella; Martin J Slade; Robert Tolhurst; Carlo Palmieri; Jie Jiang; David S Latchman; R Charles Coombes; Mustafa B A Djamgoz Journal: Clin Cancer Res Date: 2005-08-01 Impact factor: 12.531