title: Selective blockade of T-type Ca2+ channels suppresses human breast cancer cell proliferation.
abstract: We have measured the expression of T-type Ca2+ channel mRNA in breast cancer cell lines (MCF-7 (ERalpha+) using Western blot and quantitative real-time PCR (Q-RT-PCR). These results revealed that the MCF-7 cells express both alpha1G and alpha1H isoforms of T-type Ca2+ channels. In order to further clarify the role of T-type Ca2+ channels in proliferation, we tested the effects of a selective T-type Ca2+ channel inhibitor NNC-55-0396 on cellular proliferation. MCF-7 (ERalpha+) cellular proliferation was inhibited by the compound. In contrast, NNC-55-0396 at same concentration had no effect on the proliferation of MCF-10A cells, a non-cancer breast epithelial cell line. We also found that message expression of the T-type Ca2+ channels were only expressed in rapidly growing non-confluent cells but not in the cytostatic confluent cells. Knocking down the expression of T-type Ca2+ channels with siRNA targeting both alpha1G and alpha1H resulted in growth inhibition as much as 45%+/-5.0 in MCF-7 cells as compared to controls. In conclusion, our results suggest that T-type Ca2+ channel antagonism/silencing may reduce cellular proliferation in mitogenic breast cells.
authors.affiliation: Department of Pharmacology, Tulane University Health Sciences Center, New Orleans, LA 70112, USA.
authors.forename: James T
authors.initials: JT
authors.lastname: Taylor
authors.forename: Luping
authors.initials: L
authors.lastname: Huang
authors.forename: Jonathan E
authors.initials: JE
authors.lastname: Pottle
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.forename: Yali
authors.initials: Y
authors.lastname: Yang
authors.forename: Xiangbin
authors.initials: X
authors.lastname: Zeng
authors.forename: Brian M
authors.initials: BM
authors.lastname: Keyser
authors.forename: Krishna C
authors.initials: KC
authors.lastname: Agrawal
authors.forename: J Bondo
authors.initials: JB
authors.lastname: Hansen
authors.forename: Ming
authors.initials: M
authors.lastname: Li
mesh_terms: D001562:Benzimidazoles / Q000494:pharmacology*; D001940:Breast / Q000187:drug effects / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020747:Calcium Channels, T-Type / Q000378:metabolism*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D003521:Cyclopropanes; D006801:Humans; D009281:Naphthalenes; D034741:RNA, Small Interfering / Q000494:pharmacology
chemical_list: D001562:Benzimidazoles; D002121:Calcium Channel Blockers; D020747:Calcium Channels, T-Type; D003521:Cyclopropanes; D009281:Naphthalenes; D034741:RNA, Small Interfering; C484287:NNC 55-0396