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Review
, 14 (3), 211

Vitamin D and the Mammary Gland: A Review on Its Role in Normal Development and Breast Cancer

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Review

Vitamin D and the Mammary Gland: A Review on Its Role in Normal Development and Breast Cancer

Nair Lopes et al. Breast Cancer Res.

Abstract

Breast cancer is a heterogeneous disease associated with diverse biological behaviours and clinical outcome. Although some molecular subgroups of breast cancer have a targeted therapy, the most aggressive tumours still lack a molecular target. Despite vitamin D being classically associated with the physiological role of calcium regulation and phosphate transport in bone metabolism, several studies have demonstrated a wide range of functions for this hormone, which are particularly important in the field of cancer. The mechanisms underlying the protective actions of vitamin D in cancer development are only sparsely understood, but evidence shows that vitamin D participates in cell growth regulation, apoptosis and cell differentiation. In addition, it has been implicated in the suppression of cancer cell invasion, angiogenesis and metastasis. Most of vitamin D biological actions are mediated by the vitamin D receptor and the synthesis and catabolism of this hormone are regulated by the enzymes CYP27B1 and CYP24A1. In the present review we highlight research data concerning the function of this hormone in the mammary gland, with a special focus on breast carcinogenesis. Hence, and although the available data are controversial, we consider not only updated information on the epidemiology of vitamin D in breast cancer and its potential value as a therapeutic agent or prophylactic (with an emphasis on molecular mechanisms and effectors of vitamin D action), but include data on its role in other stages of breast cancer progression as well. Accordingly, we review data on the influence of vitamin D in the development of normal breast and the expression of vitamin D-related proteins (VDR, CYP27B1 and CYP24A21) in benign mammary lesions and ductal carcinomas in situ.

Figures

Figure 1
Figure 1
Representation of the differences in the expression of the vitamin D receptor, CYP27B1 and CYP24A1 during breast carcinogenesis. Vitamin D receptor (VDR) and CYP27B1 expression decreases with breast carcinogenesis, while CYP24A1 expression is augmented (brown represents positive staining). (Adapted from [26].)
Figure 2
Figure 2
Schematic view of vitamin D effects in breast cancer. C/EBPα, CCAAT enhancer binding protein alpha; CDK, cyclin dependent kinase; MMP, matrix metalloproteinase; Rb, retinoblastoma; ROS, reactive oxygen species; TNF, tumour necrosis factor; VEGF, vascular endothelial growth factor.

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