The Yin and Yang of vitamin D receptor (VDR) signaling in neoplastic progression: Operational networks and tissue-specific growth control

F.C. Campbell, Haibo Xu, M. El-Tanani, P. Crowe, V. Bingham

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68 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)1-9
Number of pages9
JournalBiochemical Pharmacology
Volume79
Issue number1
DOIs
Publication statusPublished - 01 Jan 2010

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Yin-Yang
Calcitriol Receptors
Tissue
Organ Specificity
Growth
Vitamin D
Genes
Ligands
Regulator Genes
Metabolites
Ablation
Pancreatic Neoplasms
Metabolism
Carcinogens
Tumors
Epidemiologic Studies
Prostate
Neoplasms
Carcinogenesis
Animals

Keywords

  • 1a,25-(OH)2 D3
  • Vitamin D receptor
  • Signaling
  • Cancer

Cite this

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abstract = "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.",
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AU - Xu, Haibo

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AU - Crowe, P.

AU - Bingham, V.

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