Breast cancer cell regulation by high-dose Vitamin D compounds in the absence of nuclear vitamin D receptor

The Journal of Steroid Biochemistry and Molecular Biology
Meggan Valrance, JoEllen Welsh

Abstract

1alpha,25-dihydroxyvitamin D(3) (1,25D(3)) inhibits growth and induces apoptosis in breast cancer cells in vivo and in vitro. To examine the role of the Vitamin D receptor (VDR) in mediating the actions of 1,25D(3) at nanomolar and micromolar concentrations, mammary epithelial tumor cell lines generated in wild type (WT) and VDR knockout (VDRKO) mice were utilized. WT cells express VDR and are growth inhibited by 1,25D(3) and synthetic analogs EB1089 and CB1093 at 1nM concentrations, while VDRKO cells do not express VDR and are insensitive to Vitamin D compounds at concentrations up to 100nM. In the current studies, we have confirmed and extended these previous observations. At nanomolar concentrations of 1,25D(3) and all analogs tested, including EB1089, CB1093, MC1288, and KH1230, WT cells are growth inhibited and exhibit apoptotic morphology, while VDRKO cells show no growth inhibition or apoptosis. At concentrations of 1-10microM, however, 1,25D(3) and synthetic analogs induce growth inhibition and apoptotic morphology in both WT and VDRKO cell lines. These data indicate that nanomolar concentrations of 1,25D(3) and analogs mediate growth regulatory effects via mechanisms requiring the nuclear VDR, but that micromolar conce...Continue Reading

Citations

Jan 1, 2013·ISRN Nephrology·Yu-Hsien Lai, Te-Chao Fang
Jun 14, 2005·American Journal of Physiology. Renal Physiology·Adriana S DussoEduardo Slatopolsky
May 19, 2012·Expert Review of Anticancer Therapy·Paulina SzyszkaAndrzej T Slominski
Dec 3, 2016·Hormone Molecular Biology and Clinical Investigation·Pablo R Costanzo, Pablo Knoblovits
Feb 9, 2007·Journal of Cellular Biochemistry·Meggan E ValranceJoellen Welsh
Dec 30, 2014·World Journal of Hepatology·Paula IruzubietaEmilio Fábrega
Mar 18, 2015·Physiological Reports·Ana Carolina de BragançaLúcia Andrade
Oct 17, 2019·ACS Chemical Biology·Akiko NagataMotonari Uesugi

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