Cyclin C is a primary 1alpha,25-dihydroxyvitamin D(3) responding gene.
1alpha,25-dihydroxyvitamin D(3) (VD) is a pleiotropic nuclear hormone that also has effects on cell cycle regulation. VD and its synthetic analogues are known inhibitors of cellular growth and inducers of apoptosis, however, the primary mediator genes of these effects largely remain unknown. In order to identify novel targets for VD, that may be involved in the regulation of the cell cycle, a differential display PCR (ddPCR) approach was applied to the MCF-7 human breast cancer cell line, which provided the gene for cyclin C as an interesting candidate. Quantitative assessment of cyclin C expression showed that the gene was significantly upregulated by VD and its analogues, EB1089 and CB1093 both on the level of mRNA expression and more so on the level of protein expression in MCF-7 cells. Upregulation of cyclin C protein expression could also be confirmed in MeWo human melanoma and in U937 human promyelocytic leukemia cells. This observation adds a new gene candidate to the list of primary VD responding genes. Cyclin C is not a typical cyclin, as it apparently modulates the activity of the RNA polymerase II complex, which provides fresh insight into the mechanisms of cell cycle and general transcriptional regulation by VD and its analogues.
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Institut für Physiologische Chemie I, Heinrich-Heine-Universität, D-40001 Düsseldorf, Germany.
Danielsson
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Schräder
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Carlberg
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D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects* / Q000235:genetics*; D056745:Cyclin C; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects*
C503674:CCNC protein, human; D002120:Calcium Channel Agonists; D056745:Cyclin C; D016213:Cyclins; D002117:Calcitriol