Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 1-9 |
| Number of pages | 9 |
| Journal | Biochemical Pharmacology |
| Volume | 79 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - 01 Jan 2010 |
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Keywords
- 1a,25-(OH)2 D3
- Vitamin D receptor
- Signaling
- Cancer
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The Yin and Yang of vitamin D receptor (VDR) signaling in neoplastic progression: Operational networks and tissue-specific growth control. / Campbell, F.C.; Xu, Haibo; El-Tanani, M.; Crowe, P.; Bingham, V.
In: Biochemical Pharmacology, Vol. 79, No. 1, 01.01.2010, p. 1-9.Research output: Contribution to journal › Article
TY - JOUR
T1 - The Yin and Yang of vitamin D receptor (VDR) signaling in neoplastic progression: Operational networks and tissue-specific growth control
AU - Campbell, F.C.
AU - Xu, Haibo
AU - El-Tanani, M.
AU - Crowe, P.
AU - Bingham, V.
PY - 2010/1/1
Y1 - 2010/1/1
N2 - Substantive evidence implicates vitamin D receptor (VDR) or its natural ligand 1a,25-(OH)2 D3 in modulation of tumor growth. However, both human and animal studies indicate tissue-specificity of effect. Epidemiological studies show both inverse and direct relationships between serum 25(OH)D levels and common solid cancers. VDR ablation affects carcinogen-induced tumorigenesis in a tissue-specific manner in model systems. Better understanding of the tissue-specificity of vitamin D-dependent molecular networks may provide insight into selective growth control by the seco-steroid, 1a,25-(OH)2 D3. This commentary considers complex factors that may influence the cell- or tissue-specificity of 1a,25-(OH)2 D3/VDR growth effects, including local synthesis, metabolism and transport of vitamin D and its metabolites, vitamin D receptor (VDR) expression and ligand-interactions, 1a,25-(OH)2 D3 genomic and non-genomic actions, Ca2+ flux, kinase activation, VDR interactions with activating and inhibitory vitamin D responsive elements (VDREs) within target gene promoters, VDR coregulator recruitment and differential effects on key downstream growth regulatory genes. We highlight some differences of VDR growth control relevant to colonic, esophageal, prostate, pancreatic and other cancers and assess the potential for development of selective prevention or treatment strategies.
AB - Substantive evidence implicates vitamin D receptor (VDR) or its natural ligand 1a,25-(OH)2 D3 in modulation of tumor growth. However, both human and animal studies indicate tissue-specificity of effect. Epidemiological studies show both inverse and direct relationships between serum 25(OH)D levels and common solid cancers. VDR ablation affects carcinogen-induced tumorigenesis in a tissue-specific manner in model systems. Better understanding of the tissue-specificity of vitamin D-dependent molecular networks may provide insight into selective growth control by the seco-steroid, 1a,25-(OH)2 D3. This commentary considers complex factors that may influence the cell- or tissue-specificity of 1a,25-(OH)2 D3/VDR growth effects, including local synthesis, metabolism and transport of vitamin D and its metabolites, vitamin D receptor (VDR) expression and ligand-interactions, 1a,25-(OH)2 D3 genomic and non-genomic actions, Ca2+ flux, kinase activation, VDR interactions with activating and inhibitory vitamin D responsive elements (VDREs) within target gene promoters, VDR coregulator recruitment and differential effects on key downstream growth regulatory genes. We highlight some differences of VDR growth control relevant to colonic, esophageal, prostate, pancreatic and other cancers and assess the potential for development of selective prevention or treatment strategies.
KW - 1a,25-(OH)2 D3
KW - Vitamin D receptor
KW - Signaling
KW - Cancer
UR - http://www.scopus.com/inward/record.url?scp=70350211844&partnerID=8YFLogxK
U2 - 10.1016/j.bcp.2009.09.005
DO - 10.1016/j.bcp.2009.09.005
M3 - Article
C2 - 19737544
VL - 79
SP - 1
EP - 9
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 1
ER -