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 prevented in 5 ways via the Vitamin D Receptor – Oct 2024
- Poor Vitamin D Receptor does not increase the risk of Breast Cancer (but the opposite is true) – umbrella meta-analysis Sept 2024
- An activated Vitamin D Receptor fights Autoimmune Diseases, Infections, Cancers, etc. – Dec 2023
- Breast Cancer risk reduced if consume butyrate - Dec 2023
- Breast cancer spreads to bone if poor vitamin D Receptor (no surprise) – Oct 2022
- Some breast cancers may be treated RNA changes caused by Vitamin D – March 2022
- Breast Cancer, Vitamin D, and genes – Welsh Nov 2021
- After lactation Vitamin D levels are low, increased risk of Breast Cancer, vitamin D should decrease risk – Aug 2021
- Breasts process Vitamin D and change gene activation, might prevent breast cancer if given more Vit. D – July 2021
- Breast cancer associated with Vitamin D Receptor (14th study) – Oct 2019
- After breast cancer treatment 4,000 IU of Vitamin D was not enough to help if have poor Vitamin D receptor – June 2019
- Breast Cancer death 1.8 X more likely if poor Vitamin D Receptor – April 2019
- Breast Cancer and Vitamin D review – March 2018
- Women with Breast Cancer were 16.9 times more likely to have a poor Vitamin D Receptor – Jan 2019
- Cancer treatment by Vitamin D sometimes is restricted by genes – Oct 2018
- Two chemicals increase the Vitamin D receptor and decrease the growth of breast cancer cells in the lab - March 2018
- Breast Cancer reduces receptor and thus blocks Vitamin D to the cells – several studies
- 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
- Breast Cancer incidence change by 40 percent with vitamin D receptor genes – Oct 2012
- Genes breast cancer and vitamin D receptor - Sept 2010
PDF is attached at the bottom of this page
Significance
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.
Abstract
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.