Vitamin D receptor regulates autophagy in the normal mammary gland and in luminal breast cancer cells
PNAS March 14, 2017 vol. 114 no. 11 E2186-E2194
Luz E. Tavera-Mendozaa,b,1, Thomas Westerlinga,b,1, Eric Libbyc, Andriy Marusykd, Laura Catoa,b, Raymundo Cassanie, Lisa A. Cameronf, Scott B. Ficarrog, Jarrod A. Martog, Jelena Klawitterh, and Myles Browna,b,2
- Breast Cancer Mortality reduced 60 percent if more than 60 ng of Vitamin D – meta-analysis June 2017
Pages listed in BOTH Breast Cancer AND Vitamin D Receptor
- Breast Cancer reduces receptor expression and thus block Vitamin D to the cells– July 2017
- Vitamin D receptor as a target for breast cancer therapy (abstract only) – Feb 2017
- Breast Cancer was 4.6 times more likely if have a poor Vitamin D Receptor – Dec 2016
- Increased Breast Cancer metastasis if low vitamin D or poor VDR – Feb 2016
- Increased risk of some female cancers if low vitamin D (due to genes) – meta-analysis June 2015
- Vitamin D receptor in breasts and breast cancer vary with race – March 2013
- Genes breast cancer and vitamin D receptor - Sept 2010
PDF is attached at the bottom of this page
Epidemiological evidence suggests that vitamin D can protect women from developing breast cancer (BC). This study reveals that vitamin D and its receptor regulate autophagy in both normal mammary epithelial cells and luminal Bcs, and suggests a potential mechanism underlying the link between vitamin D levels and BC risk. In addition, this work suggests that vitamin D receptor ligands could be exploited therapeutically for the treatment of a significant subset of Bcs.
Women in North America have a one in eight lifetime risk of developing breast cancer (BC), and a significant proportion of these individuals will develop recurrent BC and will eventually succumb to the disease. Metastatic, therapy-resistant BC cells are refractory to cell death induced by multiple stresses. Here, we document that the vitamin D receptor (VDR) acts as a master transcriptional regulator of autophagy. Activation of the VDR by vitamin D induces autophagy and an autophagic transcriptional signature in BC cells that correlates with increased survival in patients; strikingly, this signature is present in the normal mammary gland and is progressively lost in patients with metastatic BC. A number of epidemiological studies have shown that sufficient vitamin D serum levels might be protective against BC. We observed that dietary vitamin D supplementation in mice increases basal levels of autophagy in the normal mammary gland, highlighting the potential of vitamin D as a cancer-preventive agent. These findings point to a role of vitamin D and the VDR in modulating autophagy and cell death in both the normal mammary gland and BC cells.