1 alpha,25-dihydroxyvitamin D-3 (VD) is a pleiotropic nuclear hormone that
also has effects on cell cycle regulation. VD and its synthetic analogues a
re known inhibitors of cellular growth and inducers of apoptosis, however,
the primary mediator genes of these effects largely remain unknown. In orde
r 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 cyc
lin C as an interesting candidate. Quantitative assessment of cyclin C expr
ession showed that the gene was significantly upregulated by VD and its ana
logues, 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 U
937 human promyelocytic leukemia cells. This observation adds a new gene ca
ndidate to the list of primary VD responding genes. Cyclin C is not a typic
al cyclin, as it apparently modulates the activity of the RNA polymerase II
complex, which provides fresh insight into the mechanisms of cell cycle an
d general transcriptional regulation by VD and its analogues. J. Cell. Bioc
hem. 77:75-81, 2000. (C) 2000 Wiley-Liss, Inc.