Sensitivity to growth suppression by 1α,25-dihydroxyvitamin D3 among MCF-7 clones correlates with Vitamin D receptor protein induction

Abstract The antiproliferative effect of 1α,25-dihydroxyvitamin D 3 (1α,25(OH) 2 D 3 ) has been studied for a decade in diverse model systems, but the signalling pathways linking 1α,25(OH) 2 D 3 to cell cycle arrest remains unclear. In our attempt to establish a model system which would allow further identification of important players in the process of the 1α,25(OH) 2 D 3 imposed cell cycle arrest, we have isolated derivatives of the human breast cancer cell line MCF-7 and chosen two nearly 1α,25(OH) 2 D 3 resistant and two hypersensitive sub-clones. Investigation of cell cycle proteins regulated by 1α,25(OH) 2 D 3 in these clones indicates that activation of one component/pathway is responsible for the linkage between 1α,25(OH) 2 D 3 and growth arrest. Protein levels of the Vitamin D receptor (VDR) were elevated in sensitive cells upon 1α,25(OH) 2 D 3 treatment, whereas resistant clones were unable to induce VDR upon 1α,25(OH) 2 D 3 treatment. Our data show that VDR protein levels and the ability of a cell to induce VDR upon 1α,25(OH) 2 D 3 treatment correlate with the antiproliferative effects of 1α,25(OH) 2 D 3 , and suggest that the level of VDR in cancer cells might serve as a prognostic marker for treatment of cancer with 1α,25(OH) 2 D 3 analogues.