Page 39 - Vitamin D and Cancer

26 J. Thorne and M.J. Campbell

Abbreviations

AR Androgen receptor
bHLH Bacis helix loop helix
9 cRA 9 cis retinoic acid
1a,25(OH) D 1a,25DihydroxyvitaminD
2 3 3
DREAM Downstream regulatory element antagonist modulator
ER Estrogen receptor
FXR Farnesoid X-activated receptor
HDAC Histone deacetylase
HDACi Histone deacetylase inhibitor
HSP Heat shock protein
LCOR Ligand-dependent nuclear receptor corepressor
LCA Lithocholic acid
LXR Liver X receptor
NCOR1 Nuclear receptor corepressor 1
NCOR2/SMRT Silencing mediator of retinoid and thyroid hormone
receptors/Nuclear receptor corepressor 2
NR Nuclear receptor
PPAR Peroxisome proliferator activated receptor
RAR Retinoic acid receptor
RXR Retinoid X receptor
SLIRP SRA stem loop-interacting RNA-binding protein
SRC Steroid receptor coactivator
TRIP2/DRIP205 Thyroid hormone receptor interactor 2
TRIP15/COPS2/Alien Thyroid hormone receptor interactor 15
VDR Vitamin D receptor

2.1 Choreography of VDR Signaling

2.1.1 General Findings for VDR Transcriptional Actions

1a,25(OH) D and its precursor 25(OH)D , in common with most NR ligands, are
2
3
3
highly hydrophobic and transported in the aqueous blood stream associated with a
specific binding protein (DBP) [1–3]. At the cell membrane they are free to diffuse
across the lipid membrane, although the identification of Megalin as an active trans-
port protein for 25(OH)D suggests that transport into the cell of vitamin D
3
3
metabolites may be more tightly regulated than merely by passive diffusion alone
[4]. Once in the cells of the target organ, 1a,25(OH) D associates with the VDR.
2
3
In the absence of ligand, the VDR may be distributed throughout the cell,
although predominantly located in the nucleus. There is evidence of cytoplasmic
expression and cell-membrane-associated VDR that may mediate non-genomic