The Molecular Cancer Biology of the VDR

  • James Thorne
  • Moray J. Campbell


The development of an understanding of the role the vitamin D receptor (VDR) endocrine system plays to regulate serum calcium levels began approximately three centuries ago with the first formal descriptions of rickets. The parallel appreciation of a role for the VDR in cancer biology began approximately 3 decades ago and subsequently a remarkable increase has occurred in the understanding of its actions in normal and malignant systems.

Principally, much of this understanding has focused on understanding the extent and mechanism by which the VDR influences expression of multiple proteins whose combined actions are to govern cell cycle progression, induce differentiation, and contribute to the regulation of programmed cell death, perhaps in response to loss of genomic integrity. Predominantly, although not exclusively, these increases in target proteins reflect the transcriptional control exerted via the VDR. Reflecting the expanding understanding of how chromatin architecture is sensed and altered by transcription factors, the actions of the VDR have been defined through the large transcriptional complexes it is found in. The diversity of these complexes is large, and presumably underpins the pleiotropic biological actions that the VDR is associated with. The VDR is neither mutated nor deleted in malignancy but instead polymorphic variation distorts its ability to function, as indeed does expression of a number of associated cofactors, thereby skewing the ability to transactivate target genes.

Exploitation of this understanding into cancer therapeutic settings may occur through several routes, but perhaps a more systems orientated approach may yield insight by identifying and modeling points where the VDR, and closely related nuclear receptors, exert the most dominant control over cellular processes such as cell cycle control.


HDAC Inhibitor Lithocholic Acid Downstream Regulatory Element Antagonist Modulator ApaI Polymorphism Transcriptional Responsiveness 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Androgen receptor


Bacis helix loop helix

9 cRA

9 cis retinoic acid




Downstream regulatory element antagonist modulator


Estrogen receptor


Farnesoid X-activated receptor


Histone deacetylase


Histone deacetylase inhibitor


Heat shock protein


Ligand-dependent nuclear receptor corepressor


Lithocholic acid


Liver X receptor


Nuclear receptor corepressor 1


Silencing mediator of retinoid and thyroid hormone ­receptors/Nuclear receptor corepressor 2


Nuclear receptor


Peroxisome proliferator activated receptor


Retinoic acid receptor


Retinoid X receptor


SRA stem loop-interacting RNA-binding protein


Steroid receptor coactivator


Thyroid hormone receptor interactor 2


Thyroid hormone receptor interactor 15


Vitamin D receptor


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Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Pharmacology & TherapeuticsRoswell Park Cancer InstituteNYUSA

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