Abstract 3026: Increase in proliferation and migration of breast cancer cells via PKC activation-induced down-regulation of BKca channel

Abstract

Abstract Purpose: K+ channels are involved in tumorigenesis through the regulation of cell proliferation, apoptosis, migration, and invasion. However, the involvement of the large conductance Ca2+-activated K+ (BKCa) channels in the cancerous phenomenon is controversial. This study was performed to investigate whether and how BKCa channels are related to the cellular processes for tumorigenesis. Methods: Cell proliferation and migration assays were performed in non-invasive (MCF-7) and invasive (MDA-MB-231) breast cancer cells in the absence or presence of BKCa channel modulators or PKC modulators. Patch-clamp technique and reverse-transcriptase (RT)-polymerase chain reaction (PCR) were performed to study the expression of the BKCa channel in breast cancer cells. The relationship between BKCa channels and cell proliferation/migration was analyzed using gene overexpression and knock-down techniques. Results: Patch-clamp technique and RT-PCR data showed that BKCa channels were expressed in both MCF-7 and MDA-MB-231 cells. Inhibitors of BKCa channels increased cell proliferation and migration, whereas BKCa channel activators suppressed them. Overexpression of BKCa in breast cancer cells reduced proliferation and migration, whereas silencing of BKCa enhanced the proliferation and migration. BKCa inhibitors (paxilline, ChTx, and IbTx) induced PKC activation, and the PKC activation down-regulated the BKCa channel expression and activity. In addition, the treatment of PMA (a PKC activator) decreased BKCa channel expression, whereas combination of PKC inhibitors maintained the BKCa channel expression levels without reduction. Conclusion: These results show that a decrease in BKCa expression levels, which could be modulated by PKC activation, increases cell proliferation and migration in breast cancer cells and suggest that modulation of BKCa expression may regulate tumorigenesis of breast cancer cells. Key words: Breast cancer; Cell migration; K+ channels; Proliferation Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3026. doi:1538-7445.AM2012-3026