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Breast Cancer reduces receptor and thus blocks Vitamin D to the cells – several studies


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.
Abhishek Aggarwala, David Feldmanb, c, Brian J. Feldmana, c, ,

this study was cited 12 times as of Sept 2021

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• 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.

2010 - VDR, CYP27B1 and CYP24A

Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions
BMC Cancer volume 10, Article number: 483 (2010)
Nair Lopes, Bárbara Sousa, Diana Martins, Madalena Gomes, Daniella Vieira, Luiz A Veronese, Fernanda Milanezi, Joana Paredes, José L Costa & Fernando Schmitt
Breast cancer is a heterogeneous disease associated with different patient prognosis and responses to therapy. Vitamin D has been emerging as a potential treatment for cancer, as it has been demonstrated that it modulates proliferation, apoptosis, invasion and metastasis, among others. It acts mostly through the Vitamin D receptor (VDR) and the synthesis and degradation of this hormone are regulated by the enzymes CYP27B1 and CYP24A1, respectively. We aimed to study the expression of these three proteins by immunohistochemistry in a series of breast lesions.

We have used a cohort comprising normal breast, benign mammary lesions, carcinomas in situ and invasive carcinomas and assessed the expression of the VDR, CYP27B1 and CYP24A1 by immunohistochemistry.

The results that we have obtained show that all proteins are expressed in the various breast tissues, although at different amounts. The VDR was frequently expressed in benign lesions (93.5%) and its levels of expression were diminished in invasive tumours (56.2%). Additionally, the VDR was strongly associated with the oestrogen receptor positivity in breast carcinomas. CYP27B1 expression is slightly lower in invasive carcinomas (44.6%) than in benign lesions (55.8%). In contrast, CYP24A1 expression was augmented in carcinomas (56.0% in in situ and 53.7% in invasive carcinomas) when compared with that in benign lesions (19.0%).

From this study, we conclude that there is a deregulation of the Vitamin D signalling and metabolic pathways in breast cancer, favouring tumour progression. Thus, during mammary malignant transformation, tumour cells lose their ability to synthesize the active form of Vitamin D and respond to VDR-mediated Vitamin D effects, while increasing their ability to degrade this hormone.

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205 citations of this study as of Sept 2021

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16206 Breast Cancer reduces local Vitamin D receptor activation_compressed.pdf admin 10 Sep, 2021 15:38 438.43 Kb 11
16205 BC VDR.pdf admin 10 Sep, 2021 02:21 373.98 Kb 10
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