When assessed by a priori defined functional pathways, tumor growth factor β (TGFβ) signaling was associated with CRC risk (<i>P</i> ≤ 0.001), with most statistically significant genes being <i>SMAD7 (P<sub>BH</sub></i> = 0.008) and <i>SMAD3 (P<sub>BH</sub></i> = 0.008), and 18 SNPs in the vitamin D receptor (VDR) binding sites (<i>P</i> = 0.036).
We found that positive VDR expression in the nuclei and cytoplasm of breast cancer cells was associated with favorable tumor characteristics such as smaller size, lower grade, estrogen receptor positivity and progesterone receptor positivity, and lower expression of Ki67.
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.
Vitamin D3 is known to have anticancer actions by affecting tumorigenesis including the cell cycle and cell apoptosis in gastric cancer (GC) cells; the genes including microRNAs (miRNAs) regulated by vitamin D3 signaling remain discovered. miR-99b-3p, the tumor suppressor gene, is not only decreased in GC tissues, but is also induced by vitamin D3 through the vitamin D receptor (VDR) binding on the promoter domain of miR-99b.
Loss of the VDR in human breast cancer cells marks a critical point in oncogenesis by inducing EMT, promoting the dissemination of cancer cells, and facilitating the formation of tumor colonies in bone.
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.
The vitamin D receptor (VDR) is expressed in the tumor stroma and treatment with VDR ligands results in stromal remodeling and increased intratumoral gemcitabine delivery.
Taken together, these findings confirmed that VDR functions as a tumour suppressor in RCC cells and suppresses the proliferation, migration and invasion of RCC through regulating the expression of TRPV5.
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.
Here, we report on the unexpected finding that stable knockdown of VDR expression in the human breast and prostate cancer cell lines, MDA-MB-231 and PC3, strongly induces cell apoptosis and inhibits cell proliferation <i>in vitro.</i> Implantation of these VDR knockdown cells into the mammary fat pad (MDA-MB-231), subcutaneously (PC3) or intra-tibially (both cell lines) in immune-incompetent nude mice resulted in reduced tumor growth associated with increased apoptosis and reduced cell proliferation compared with controls.
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.
In the present study we assess whether vitamin D supplementation, in the follow-up period after diagnosis and surgical resection of the primary tumor, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and Vitamin D Receptor immunoreactivity in the primary tumor.
Model systems of carcinogenesis have provided evidence that both VDR expression and 1,25D actions change with transformation but clinical data regarding vitamin D responsiveness of established tumors is limited and inconclusive.
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.
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.