title: Reduction of breast cancer cell migration via up-regulation of TASK-3 two-pore domain K+ channel.
abstract: OBJECTIVE
  Many kinds of K(+) channels are expressed in a variety of cells, including cancer cells. However, only a small amount of research has explored the relationship between voltage-independent K(+) channels and breast cancer. This study was performed to investigate whether changes in two-pore domain K(+) (K(2P) ) channel expression levels are related to the migration of human breast cancer cells.
  
  
  METHODS
  K(2P) channel gene/protein expression levels were compared between MCF-7 (a non-invasive cell) and MDA-MB-231 (an invasive cell) using reverse transcriptase (RT)-polymerase chain reaction (PCR), real-time PCR, Western blotting and immunocytochemistry. The relationship between K(2P) channel expression level and cell migration was analysed using gene overexpression and knock-down techniques. Functional expression of TASK-3 in MCF-7 and MDA-MB-231 cells was recorded using patch-clamp technique.
  
  
  RESULTS
  Of K(2P) channels, TASK-3 mRNA and protein were highly expressed in MCF-7 cells compared with those in MDA-MB-231 cells. Overexpression of TASK-3 in breast cancer cells reduced migration and invasion, whereas silencing of TASK-3 increased the migration and invasion. The TASK-3 expression level was decreased by phorbol myristate acetate (PMA), a PKC activator. PMA also enhanced the cell migration in MDA-MB-231 cells.
  
  
  CONCLUSIONS
  These results show that an increase in TASK-3 expression levels, which could be modulated by PKC activation, reduces cell migration/invasion in breast cancer cells and suggest that modulation of TASK-3 expression may regulate metastasis of breast cancer cells.
authors.affiliation: Division of Hematology-Oncology, Department of Internal Medicine, Gyeongsang National University Hospital, Jinju, South Korea.
authors.forename: G-W
authors.initials: GW
authors.lastname: Lee
authors.forename: H S
authors.initials: HS
authors.lastname: Park
authors.forename: E-J
authors.initials: EJ
authors.lastname: Kim
authors.forename: Y-W
authors.initials: YW
authors.lastname: Cho
authors.forename: G-T
authors.initials: GT
authors.lastname: Kim
authors.forename: Y-J
authors.initials: YJ
authors.lastname: Mun
authors.forename: E-J
authors.initials: EJ
authors.lastname: Choi
authors.forename: J-S
authors.initials: JS
authors.lastname: Lee
authors.forename: J
authors.initials: J
authors.lastname: Han
authors.forename: D
authors.initials: D
authors.lastname: Kang
mesh_terms: D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D009361:Neoplasm Invasiveness / Q000235:genetics*; D018408:Patch-Clamp Techniques; D024683:Potassium Channels, Tandem Pore Domain / Q000235:genetics / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation
chemical_list: C498655:KCNK9 protein, human; D024683:Potassium Channels, Tandem Pore Domain; D034741:RNA, Small Interfering; D011493:Protein Kinase C