Vitamin D-3 receptor as a target for breast cancer prevention.
The vitamin D-3 receptor (VDR) is a nuclear receptor that modulates gene expression when complexed with its ligand 1-alpha,25-dihydroxycholecalciferol [1,25(OH)(2)-D(3)], which is the biologically active form of vitamin D-3. The cellular effects of VDR signaling include growth arrest, differentiation and/or induction of apoptosis, which indicate that the vitamin D pathway participates in negative-growth regulation. Although much attention has been directed in recent years toward the development of synthetic vitamin D analogs as therapeutic agents for a variety of human cancers including those derived from the mammary gland, studies on vitamin D as a chemopreventive agent for breast cancer have been quite limited. The VDR is expressed in normal mammary gland, where it functions to oppose estrogen-driven proliferation and maintain differentiation; this suggests that 1,25(OH)(2)-D(3) participates in negative-growth regulation of mammary epithelial cells. Furthermore, preclinical studies show that vitamin D compounds can reduce breast cancer development in animals, and human data indicate that both vitamin D status and genetic variations in the VDR may affect breast cancer risk. Collectively, findings from cellular, molecular and population studies suggest that the VDR is a nutritionally modulated growth-regulatory gene that may represent a molecular target for chemoprevention of breast cancer.
Welsh
JoEllen
J
Department of Biological Sciences, University of Notre Dame, Notre Dame, IN 46556, USA. jwelsh3@nd.edu
Wietzke
Jennifer A
JA
Zinser
Glendon M
GM
Byrne
Belinda
B
Smith
Kelly
K
Narvaez
Carmen J
CJ
D000818:Animals; D001940:Breast / Q000378:metabolism; D001943:Breast Neoplasms / Q000517:prevention & control*; D002762:Cholecalciferol / Q000378:metabolism / Q000502:physiology; D005260:Female; D006801:Humans; D008297:Male; D015674:Mammary Neoplasms, Animal / Q000517:prevention & control*; D051379:Mice; D018345:Mice, Knockout; D008967:Molecular Biology; D018167:Receptors, Calcitriol / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D014407:Tumor Cells, Cultured; D014807:Vitamin D / Q000378:metabolism / Q000502:physiology / Q000627:therapeutic use
D018167:Receptors, Calcitriol; D014807:Vitamin D; D002762:Cholecalciferol