Abstract

Resistance to antiestrogens is a major clinical problem in current breast cancer treatment and development of new treatment strategies for these tumors is highly prioritized. In this study, we have investigated the effects of 1 alpha,25-dihydroxyvitamin D-3 on the proliferation of tamoxifen-resistant cells. Further, we have investigated on a molecular level the effects of vitamin D on NF kappa B signaling in tamoxifen-resistant breast cancer cells. Parental human breast cancer MCF-7 cells and four tamoxifen-resistant sublines have been used to investigate the effects of 1 alpha,25-dihydroxyvitamin 133 on cell proliferation using a colorimetric method, gene expression using quantitative PCR, protein phosphorylation using Western blot analysis and cellular localization of proteins using immunofluorescence microscopy. We found that 1 alpha,25-dihydroxyvitamin D-3 is able to strongly decrease the growth of both tamoxifen-sensitive and -resistant breast cancer cells and that this antiproliferative effect of 1 alpha,25-dihydroxyvitamin D-3 might be mediated via inhibition of the NF kappa B pathway. We found that 1 alpha,25-dihydroxyvitamin D-3 stimulates the gene expression of IkB, an NM-inhibiting protein, and that cells pretreated with 1 alpha,25-dihydroxyvitamin D-3 have a decreased sensitivity to TNF alpha stimulation. Further, we show that 1 alpha,25-dihydroxyvitamin D-3 treatment strongly decreases the TNF alpha-induced translocation of p65 into the nucleus. This manuscript reports novel findings regarding the effects of 1 alpha,25-dihydroxyvitamin D-3 on NF kappa B signaling in tamoxifen-resistant breast cancer cells and suggests that vitamin D might be interesting for further evaluation as a new strategy to treat antiestrogen-resistant breast cancers. (C) 2014 Elsevier Inc. All rights reserved.

Keywords

Breast cancer; Tamoxifen-resistance; Vitamin D; 1 alpha,25-Dihydroxyvitamin D-3

Published in

Steroids
2014, Volume: 85, pages: 30-35

SLU Authors

• Lundqvist, Johan

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    
  • Danish Cancer Society Research Center

Sustainable Development Goals

SDG3 Ensure healthy lives and promote well-being for all at all ages


UKÄ Subject classification

Cell and Molecular Biology
Cancer and Oncology
Pharmacology and Toxicology


Publication identifier

DOI: https://doi.org/10.1016/j.steroids.2014.04.001

Permanent link to this page (URI)

https://res.slu.se/id/publ/53548