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Perhaps most, but not all, types of Breast Cancer are helped by Vitamin D – March 2017

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


Pages listed in BOTH Breast Cancer AND Vitamin D Receptor

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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.

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