Abstract
Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR). It regulates the action of hormone responsive genes and is involved in cell cycle regulation, differentiation and apoptosis. VDR is a critical component of the vitamin D pathway and different common single nucleotide polymorphisms have been identified. Cdx2 VDR polymorphism can play an important role in breast cancer, modulating the activity of VDR. The objective of this study is to assess the relationship between the Cdx2 VDR polymorphism and the activities of VDR in human breast cancer cell lines and carcinomas breast patients. Cdx2 VDR polymorphism and antiproliferative effects of vitamin D treatment were investigated in a panel of estrogen receptor-positive (MCF7 and T-47D) and estrogen receptor-negative (MDA-MB-231, SUM 159PT, SK-BR-3, BT549, MDA-MB-468, HCC1143, BT20 and HCC1954) human breast cancer cell lines. Furthermore, the potential relationship among Cdx2 VDR polymorphism and a number of biomarkers used in clinical management of breast cancer was assessed in an ad hoc set of breast cancer cases. Vitamin D treatment efficacy was found to be strongly dependent on the Cdx2 VDR status in ER-negative breast cancer cell lines tested. In our series of breast cancer cases, the results indicated that patients with variant homozygote AA were associated with bio-pathological characteristics typical of more aggressive tumours, such as ER negative, HER2 positive and G3. Our results may suggest a potential effect of Cdx2 VDR polymorphism on the efficacy of vitamin D treatment in aggressive breast cancer cells (estrogen receptor negative). These results suggest that Cdx2 polymorphism may be a potential biomarker for vitamin D treatment in breast cancer, independently of the VDR receptor expression.
Highlights
Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR), a nuclear transcriptional factor which belongs to the super family of steroid/thyroid hormone receptors [1,2]
We explored the association between Cdx2 polymorphism and VDR immunohistochemical expression in an ad hoc retrospective series of 80 human breast carcinomas taking into account breast cancer molecular classification (Luminal A, Luminal B, HER2-Subtype (HS), and Triple Negative) and clinical-pathological parameters routinely detected in breast cancer management
We evaluated the relative vdr mRNA and VDR protein expression in the 10 breast cancer (BC) cell lines previously genotyped for Cdx2 polymorphism (Fig 1)
Summary
Vitamin D plays a role in cancer development and acts through the vitamin D receptor (VDR), a nuclear transcriptional factor which belongs to the super family of steroid/thyroid hormone receptors [1,2]. Slominski et al [6] recently have provided robust evidences that a novel pathway of D3 metabolism operates in vivo that is initiated and regulated by P450scc, modified by CYP27B1, and of which the products and intermediates are biologically active. These products act as partial agonists of the VDR and determinate the translocation of VDR from the cytoplasm to the nucleus with a potency comparable to the 1,25(OH)2D3 [7]
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