Page 292 - Vitamin D and Cancer

Chapter 12
The Vitamin D Signaling Pathway in Mammary
Gland and Breast Cancer

Glendon M. Zinser, Carmen J. Narvaez, and JoEllen Welsh

Abstract Epidemiologic data have demonstrated that breast cancer incidence
is inversely correlated with indices of vitamin D status, including UV exposure,
which enhances epidermal vitamin D synthesis. The vitamin D receptor (VDR)
is expressed in mammary epithelial cells, suggesting that vitamin D may directly
influence sensitivity of the gland to transformation. Consistent with this concept,
in vitro studies have demonstrated that the VDR ligand, 1,25-dihydroxyvitamin
D (1,25D), exerts negative growth regulatory effects on mammary epithelial cells
that contribute to maintain the differentiated phenotype and protection of the
genome. Mammary cells also have the ability to internalize the major circulat-
ing vitamin D metabolite, 25-hydroxyvitamin D (25D), and convert it to 1,25D.
Furthermore, deletion of the VDR gene in mice alters the balance between
proliferation and apoptosis in the mammary gland which ultimately enhances
its susceptibility to carcinogenesis. Dietary supplementation with vitamin D, or
chronic treatment with synthetic VDR agonists, reduces the incidence of carcin-
ogen-induced mammary tumors in rodents. Collectively, these observations have
reinforced the need to further define the human requirement for vitamin D and
the molecular actions of the VDR in relation to prevention of breast cancer.

Keywords Vitamin D receptor • Breast cancer • Mammary gland • Vitamin D
• Prevention

J. Welsh (*)
GenNYsis Center for Excellence in Cancer Genomics, University of Albany, Rensselaer,
NY 12144, USA
e-mail: jwelsh@albany.edu

D.L. Trump and C.S. Johnson (eds.), Vitamin D and Cancer, 279
DOI 10.1007/978-1-4419-7188-3_12, © Springer Science+Business Media, LLC 2011