Proceedings of the Nutrition Society

Research Article

The vitamin D receptor in cancer

Symposium on ‘Diet and cancer’

on 16–19 July 2007, The Summer Meeting of the Nutrition Society, was held at the University of Ulster, Coleraine, hosted by the Irish Section.

James Thornea1 c1 and Moray J. Campbella1a2

a1 Institute of Biomedical Research, Wolfson Drive, University of Birmingham Medical School, Edgbaston B15 2TT, UK

a2 Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA

Abstract

Over the last 25 years roles have been established for vitamin D receptor (VDR) in influencing cell proliferation and differentiation. For example, murine knock-out approaches have revealed a role for the VDR in controlling mammary gland growth and function. These actions appear widespread, as the enzymes responsible for 1α,25-dihydroxycholecalciferol generation and degradation, and the VDR itself, are all functionally present in a wide range of epithelial and haematopoietic cell types. These findings, combined with epidemiological and functional data, support the concept that local, autocrine and paracrine VDR signalling exerts control over cell-fate decisions in multiple cell types. Furthermore, the recent identification of bile acid lithocholic acid as a VDR ligand underscores the environmental sensing role for the VDR. In vitro and in vivo dissection of VDR signalling in cancers (e.g. breast, prostate and colon) supports a role for targeting the VDR in either chemoprevention or chemotherapy settings. As with other potential therapeutics, it has become clear that cancer cells display de novo and acquired genetic and epigenetic mechanisms of resistance to these actions. Consequently, a range of experimental and clinical options are being developed to bring about more targeted actions, overcome resistance and enhance the efficacy of VDR-centred therapeutics.

Correspondence:

c1 Corresponding author: Dr James Thorne, fax +44 121 4158712, email j.thorne@bham.ac.uk