Vitamin D3 signaling and breast cancer: Insights from transgenic mouse models. Issue 178 (April 2018)

• Record Type: Journal Article
• Authors: Sheng, Lei; Callen, David F.; Turner, Andrew G.
• Is Part Of: Journal of steroid biochemistry and molecular biology. Issue 178(2017)
• Page Start: 348
• Page End: 353
• Publication Date: 2018-04
• Subjects: Breast cancer -- Vitamin D3 -- Cyp27b1 -- Cyp24a1 -- Vitamin D3 receptor; Steroid hormones -- Periodicals; Biochemistry -- Periodicals; Hormones -- Periodicals; Molecular Biology -- Periodicals; Hormones stéroïdes -- Périodiques; Steroid hormones; Periodicals; 572.579
• DOI: 10.1016/j.jsbmb.2018.02.006
• Languages: English
• ISSNs: 0960-0760

Abstract

Highlights: Pre-clinical studies highlight roles for vitamin D3 in protection against breast cancer. Vitamin D3 receptor is essential for a functional vitamin D3 signaling pathway. Locally produced 1, 25(OH)2 D by Cyp27b1 is critical for inhibiting tumor growth. Cyp24a1 is a potential target for breast cancer prevention and/or treatment. Abstract: The biologically active form of vitamin D3 (1, 25(OH)2 D) regulates epithelial cell differentiation, proliferation, and apoptosis, lending weight to clinical evidence linking vitamin D3 insufficiency to breast cancer incidence and mortality. Local dysregulation of vitamin D3 metabolism has been identified in patients with breast cancer, implying that disruption of 1, 25(OH)2 D signaling may contribute to breast cancer development in an autocrine or paracrine manner. Mouse mammary glands express the critical enzymes responsible for 1, 25(OH)2 D synthesis (Cyp2r1 and Cyp27b1), degradation (Cyp24a1), as well as the vitamin D3 receptor (Vdr), and genetically modified mouse models have revealed a great deal about the role of vitamin D3 in cancer initiation and progression. Ablation of Vdr or Cyp27b1 in murine models of mammary cancer reduces the anti-tumor effects of vitamin D3, while elevation of Cyp24a1 levels increases degradation of 1, 25(OH)2 D, leading to diminished anti-tumor effects. This review discusses the recent transgenic mouse models of vitamin D3 metabolism and the Vdr signaling network, and how these contribute to mammary gland development, and cancer tumorigenesis and progression. Collectively, these mouse models have helped clarify mechanisms of action of vitamin D3 signaling and suggest that activation or restoration of the vitamin D3 regulated pathway is a potential approach for human breast cancer prevention.