(i) Measure the expression of CYP27B1, CYP24A1, and vitamin D3 receptor in human nonmalignant and cholangiocarcinoma lines and biopsy control or tumour samples; and (ii) evaluate the effects of vitamin D3 on vitamin D3 synthesis and cholangiocarcinoma growth.
Vitamin D receptor (VDR) expression has been shown to be upregulated in several tumors and is supposed to represent an important endogenous response to tumor progression.
VDR expression was inversely related to aggressive tumor characteristics, including large tumor size, hormonal receptor (HR) negativity, and triple-negative subtype (P < 0.05).
Vitamin D receptor (VDR) polymorphisms are found more commonly in some tumor types than in healthy individuals, suggesting that some polymorphisms (Cdx2, Fok1, Bsm1, Apa1, Taq1) contribute to tumor development.
A similar increased ratio of corepressor mRNA to VDR occurred in matched primary tumor and normal cells, noticeably in estrogen receptor alpha-negative (n = 7) tumors.
Although the compounds induced hypercalcemia at elevated doses, consistent with VDR agonism in vivo, they both reduced tumor burden at doses below their MTD's.
Because the levels of VDR in MCF-7 breast cancer cells correlate with the antiproliferative effects of 1,25(OH)(2)D(3) and because C/EBPalpha has been suggested as a potential tumor suppressor in breast cancer, these findings provide important mechanisms whereby 1,25(OH)(2)D(3) may act to inhibit growth of breast cancer cells.
Consequently, we evaluated serum 25(OH) D levels, vitamin D receptor (VDR) polymorphisms and the methylation status of the tumor suppressor gene dickkopf homolog 1 (DKK1) as risk factors for colon polyp in this population.
Considering the rising incidence of breast cancer and high prevalence of vitamin D deficiency, this review aimed to reflect an association between serum vitamin D concentration and breast cancer risk, reveal the link between vitamin D receptor genetic polymorphisms and breast cancer risk, and review the relationship between vitamin D level, breast cancer risk, and prognostic factors such as tumor stage, grade, size, lymph node involvement, and hormone receptor status.
Emerging evidence suggests that the normally tight balance between CYP27B1 and CYP24A1 becomes deregulated during cancer development, leading to abrogation of the tumor suppressive effects triggered by VDR.
Further investigation revealed that compound 28 inhibited tumor growth in an orthotopic breast-tumor model without causing hypercalcemia which is the main side effect of secosteroidal VDR modulators.
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.
Here we show by immunohistochemistry and RNAscope in situ hybridization that vitamin D receptor (VDR) is unexpectedly expressed in LGR5<sup>+</sup> colon stem cells in human tissue and in normal and tumor organoid cultures generated from patient biopsies.