The Vitamin D3 Pathway in Human Skin and its Role for Regulation of Biological Processes, 2005
Wavelength-Dependent Induction of CYP24A1-mRNA after UVB-Triggered Calcitriol Synthesis in Cultured Human Keratinocytes, 2006
In contrast, UVB and calcitriol had no effect on gene expression of CYP27A1 and CYP27B1. We conclude from these experiments a constitutive gene expression of the vitamin D3 hydroxylases, whereas the catabolic enzyme CYP24A1 is markedly regulated by UVB, calcitriol, and perhaps cell proliferation.
Cell cycle-associated CYP24A1 gene expression after or without a normal medium change. Cell cycle-associated transient CYP24A1-mRNA induction in non-irradiated keratinocytes after a normal medium change and constitutive CYP24A1-mRNA expression during basal proliferation activity in keratinocytes without medium change. The strong but transient CYP24A1-mRNA induction at 8 hours after a normal medium change is followed by an increased percentage of keratinocytes going through the S phase, whereas keratinocytes incubated without any medium change at 0 hour show constitutive expression levels as well as basal proliferation activity as determined by FACS cell cycle analysis: standardized relative gene expression of CYP24A1 expressed as a ratio of copies of CYP24A1-mRNA and copies of GAPDH-mRNA; expression level of non-irradiated control keratinocytes was defined as reference expression level=1.0 (left y axis); percentage of keratinocytes passing the S phase (right y axis). Real-time PCR data presented here are based on one representative series. FACS data presented are based on one series.
CYP24A1 Is an Independent Prognostic Marker of Survival in Patients with Lung Adenocarcinoma 2011
CYP24A1 mRNA was elevated 8- to 50-fold in lung AC (compared to normal nonneoplastic lung) and significantly higher in poorly differentiated cancers. At 5 years of follow-up, the probability of survival was 42% (high CYP24A1, n = 29) versus 81% (low CYP24A1, n = 57) (P = 0.007). The validation set of 101 tumors showed that CYP24A1 was independently prognostic of survival (multivariate Cox model adjusted for age, gender, and stage, P = 0.001). A549 cells (high CYP24A1) were more resistant to antiproliferative effects of 1,25-D3 compared with SKLU-1 cells (low CYP24A1).
VITAMIN D - CYP24, Cardiff University
The common antiproliferative VDR functions are associated with arrest in G0/G1 of the cell cycle, and with the upregulation of a number of cell cycle inhibitors including p21waf/cip1 and p27kip1. Calcitriol also mediates a G2/M cell cycle arrest through the direct induction of the growth arrest and DNA damage gene GADD45a. Our established Birmingham-Cardiff CYP24 programme allowed us to explore the effects of calcitriol + CYP24A1 inhibitor on VDR signaling. The exciting preliminary data generated from this collaboration has recently been published (Yee et al 2006) and provided proof of concept, with enhanced antiproliferative activity observed and upregulation of VDR genes CYP24A1, p21waf1/cip1 and GADD45a.
CYP24A1 Inhibitors
