title: Calcium regulates caveolin-1 expression at the transcriptional level.
abstract: Caveolin-1, an indispensable component of caveolae serving as a transformation suppressor protein, is highly expressed in poorly metastatic mouse osteosarcoma FBJ-S1 cells while highly metastatic FBJ-LL cells express low levels of caveolin-1. Calcium concentration is higher in FBJ-S1 cells than in FBJ-LL cells; therefore, we investigated the possibility that calcium signaling positively regulates caveolin-1 in mouse FBJ-S1 cells. When cells were treated with the calcium channel blocker nifedipine, cyclosporin A (a calcineurin inhibitor), or INCA-6 (a nuclear factor of activated T-cells [NFAT] inhibitor), caveolin-1 expression at the mRNA and protein levels decreased. RNA silencing of voltage-dependent L-type calcium channel subunit alpha-1C resulted in suppression of caveolin-1 expression. This novel caveolin-1 regulation pathway was also identified in mouse NIH 3T3 cells and Lewis lung carcinoma cells. These results indicate that caveolin-1 is positively regulated at the transcriptional level through a novel calcium signaling pathway mediated by L-type calcium channel/Ca(2+)/calcineurin/NFAT.
authors.affiliation: Laboratory of Tumor Biology and Glycobiology, Department of Life Sciences, Shenyang Pharmaceutical University, Shenyang 110016, People's Republic of China.
authors.forename: Xiao-Yan
authors.initials: XY
authors.lastname: Yang
authors.forename: Cheng-Cheng
authors.initials: CC
authors.lastname: Huang
authors.forename: Qi-Ming
authors.initials: QM
authors.lastname: Kan
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Dan
authors.initials: D
authors.lastname: Liu
authors.forename: Xue-Cheng
authors.initials: XC
authors.lastname: Zhang
authors.forename: Toshinori
authors.initials: T
authors.lastname: Sato
authors.forename: Sadako
authors.initials: S
authors.lastname: Yamagata
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Yamagata
mesh_terms: D000818:Animals; D019703:Calcineurin / Q000378:metabolism; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism; D020013:Calcium Signaling; D051242:Caveolin 1 / Q000235:genetics*; D045744:Cell Line, Tumor; D051379:Mice; D050778:NFATC Transcription Factors; D014158:Transcription, Genetic
chemical_list: D020746:Calcium Channels, L-Type; D051242:Caveolin 1; D050778:NFATC Transcription Factors; D019703:Calcineurin; D002118:Calcium