Identification of tumor-autonomous and indirect effects of vitamin D action that inhibit breast cancer growth and tumor progression
The Journal of Steroid Biochemistry and Molecular Biology. online 11 July 2017. https://doi.org/10.1016/j.jsbmb.201, 7.07.003
Abhishek Aggarwala, David Feldmanb, c, Brian J. Feldmana, c, ,
- 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 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
• Epidemiological data suggests an inverse correlation between vitamin D deficiency and breast cancer risk.
• Tumor-autonomous effects of vitamin D signaling suppress breast cancer metastases.
• Tumor-autonomous dysregulation of Id1 expression with vitamin D deficiency is sufficient to promote metastatic spread.
Several epidemiological studies have found that low vitamin D levels are associated with worse prognosis and poorer outcomes in patients with breast cancer (BCa), although some studies have failed to find this association. In addition, prior research has found that BCa patients with vitamin D deficiency have a more aggressive molecular phenotype and worse prognostic biomarkers.
As vitamin D deficiency is common in patients diagnosed with BCa, elucidating the cause of the association between poor outcomes and vitamin D deficiency promises to have a significant impact on improving care for patients with BCa including enabling the development of novel therapeutic approaches.
Here we review our recent findings in this area, including our data revealing that reduction of the expression of the vitamin D receptor (Vdr) within BCa cells accelerates primary tumor growth and enables the development of metastases, demonstrating a tumor autonomous effect of vitamin D signaling to suppress BCa metastases. We believe that these findings are likely relevant to humans as we discovered evidence that a mechanism of VDR regulation identified in our mouse models is conserved in human BCa. In particular, we identified a negative correlation between serum 25(OH)D concentration and the level of expression of the tumor progression factor ID1 in primary tumors from patients with breast cancer.
calcitriol, 1α, 25-dihydroxyvitamin D3; 25(OH)D, 25-hydroxyvitamin vitamin D; CYP27B1, 1α, -hydroxylase; VDR, vitamin D receptor; RXR, retinoid X receptor; VDRE, vitamin D response element; ID1, Inhibitor of Differentiation 1; OVX, ovariectomized; BCa, breast cancer