Vitamin D receptors in breast cancer cells

Abstract

1,25-(OH)2-Vitamin D3, the active metabolite of vitamin D, is a secosteroid hormone with known differentiating activity in leukemic cells. Studies have demonstrated the presence of vitamin D receptors (VDR) in a wide range of tissues and cell types. Antiproliferative activity of 1,25-(OH)2-vitamin D3 has been documented in osteosarcoma, melanoma, colon carcinoma, and breast carcinoma cells. This study was designed to analyze vitamin D receptor level in breast cancer cells as a marker of differentiation and as a predictor of growth inhibition by 1,25-(OH)2-vitamin D3. VDR messenger RNA was found to be present in relatively high levels in well-differentiated cells and in low levels in poorly differentiated cells. All cell lines had detectable VDR mRNA. Radiolabeled ligand binding assay showed a similar pattern. MCF-7 and T47D cells, which express VDR at moderate levels, showed significant growth inhibition by 10(-9) M1,25-(OH)2-vitamin D3 (p < 0.05). MDA-MB-231 cells, which have very low levels of VDR, demonstrated no growth inhibition by 1,25-(OH)2-vitamin D3 at concentrations up to 10(-6) M. Based on these results it can be stated that VDR expression is lost with de-differentiation and that receptor is essential for the antiproliferative response to 1,25-(OH)2-vitamin D3.

Ultrafiolett stråling og sykdomsrisiko

“…De demonstrerte hvordan kalsitriol hemmer celledeling og øker differensieringen av kreftceller. Flere eksperimentelle studier viser at kalsitriol også fremmer celledød og hemmer tumorvekst (16,(20)(21)(22)(23). Epidemiologiske studier viser at forekomsten og dødeligheten av kreft i bryst, prostata og tykktarm er større i nord sammenlignet med i sør, og man tror at forskjeller i UVeksponering og i vitamin D-nivå kan forklare disse resultatene (24)(25)(26)(27)(28).…”

“…Både de eksperimentelle og epidemiologiske studiene indikerer at vitamin D kan hemme progresjon av visse kreftformer og at et høyt vitamin D-nivå kan bedre prognosen ved en kreftsykdom. Det er også studier som indikerer at vitamin D samvirker med og øker effekten av strålebehandling og dermed øker overlevelsen ved kreftsykdom (21,30).…”

Androgen and vitamin D receptor expression in archival human breast tumors

“…Freake et al (6) found that, in human breast tumor cells, VDR expression is at concentrations higher than previously described, and Bu-ras et al (13) reported that high VDR expression is seen in well-differentiated tumors as compared with less differentiated tumors.…”

Mechanism of Action of a Novel Analog of Vitamin D3 1 Alpha-hydroxy-24-ethyl Cholecalciferol (D5) in Normal and Transformed Human Breast Epithelial Cells

“…Earlier, the VDR was found to be present in abundance in intestine, bone, liver, and kidney cells. Aside from the classical target organs, the VDR has now been isolated from a variety of tissues including normal mammary epithelium as well as breast tumors (Buras et al, 1994;Eisman et al, 1980).…”

“…Earlier, the VDR was found to be present in abundance in intestine, bone, liver, and kidney cells. Aside from the classical target organs, the VDR has now been isolated from a variety of tissues including normal mammary epithelium as well as breast tumors (Buras et al, 1994;Eisman et al, 1980).In order for VDR to function, it needs to interact with vitamin D response elements (VDRE) and bind to DNA to initiate or repress transcription . VDR must form a dimer to stabilize VDRE transactivation (Jones et al, 1998).…”