Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1,25(OH)2-Vitamin D3 inhibits breast cancer cell proliferation through interaction with the vitamin D receptor (VDR). Regulation of VDR is under the influence of several factors which include the functional ligand for this receptor (1,25(OH)2-vitamin D3) as well as heterologous steroid hormones. We evaluated the nature of homologous regulation in T-47D human breast cancer cells with a radiolabelled ligand binding assay and a ribonuclease protection assay for VDR. Significant VDR up-regulation, as measured by hormone binding assays, occurred with pre-incubations with 10(-9)M through 10(-6)M 1,25(OH)2-vitamin D3 (P < 0.05). A 7-fold VDR up-regulation with 10(-8)M 1,25(OH)2-vitamin D3 occurred at 4 h treatment and was not associated with an increase in VDR mRNA expression on ribonuclease protection assay. This supports the hypothesis that up-regulation of VDR is probably the result of ligand-induced stabilization of pre-existing receptor. All-trans-retinoic acid, the progesterone analog R-5020, and prednisone were found to induce heterologous up-regulation of the VDR. We then determined with ligand binding assays whether 1,25(OH)2-vitamin D3 could influence receptor levels for another hormone in a manner analogous to the heterologous regulation of VDR. Regulation of estrogen receptor (ER) by 1,25(OH)2-vitamin D3 was studied in T-47D and MDA-MB-231 breast cancer cells. Incubation of T-47D cells, which are ER (+), with 10(-8)M 1,25(OH)2-vitamin D3 did not result in up-regulation of ER. Yet estrogen binding was significantly up-regulated in a cell line that is ER(-), MDA-MB-231. The increased estrogen binding was associated with a shift in binding affinity and ribonuclease protection assay showed absence of ER mRNA in these cells, suggesting an up-regulation of estrogen binding proteins and not of the ER itself.
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PMID:Modulation of vitamin D receptor and estrogen receptor by 1,25(OH)2-vitamin D3 in T-47D human breast cancer cells. 766 88

The natural biologically active form of vitamin D3, 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), possesses antiproliferative, prodifferentiating and immunomodulatory properties. The actions of 1,25(OH)2D3 are mediated through the intracellular vitamin D receptor (VDR), and the level of VDR is believed to determine the cellular responsiveness to vitamin D3. In the present study we examined the effects of 1,25(OH)2D3 on the expression of VDR and its message in cultured human keratinocytes. Western analysis showed the mean VDR content to be higher in undifferentiated cultures (175 pg/microgram protein) than in differentiated cultures (90 pg/microgram protein). Incubation with 1,25(OH)2D3 induced an increase in the VDR in both undifferentiated and differentiated keratinocytes. The VDR increase was detectable after 2 h and maximal (approximately two-fold stimulation) after 8 h. The 1,25(OH)2D3-induced stimulation of VDR levels was dose dependent with a maximum at 10(-7) M. The VDR mRNA levels as determined by the ribonuclease protection assay showed a peak (50% stimulation) after approximately 2 h. Although this increase in VDR mRNA was not statistically significant, the results indicate that the ligand-induced upregulation of VDR involves increased transcription. The upregulation of VDR levels may increase the responsiveness to 1,25(OH)2D3 and may, therefore, be an important mechanism for regulating the effects of 1,25(OH)2D3 on keratinocyte proliferation and differentiation.
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PMID:Upregulation of vitamin D receptor levels by 1,25(OH)2 vitamin D3 in cultured human keratinocytes. 920 84

Treatment with vitamin D3 analogs improves psoriasis. The vitamin D receptor (VDR) mediates most, if not all, the effects of vitamin D3. The purpose of this study was to determine the levels of the VDR mRNA and VDR protein in normal and in involved and uninvolved psoriatic skin. Although VDR mRNA was not detected by Northern analysis of human skin samples, it was readily detectable by use of the more sensitive ribonuclease protection assay. The VDR mRNA levels were normal in acute guttate as well as in chronic plaque lesions. There was also no difference in VDR mRNA levels between normal and uninvolved psoriatic skin. The VDR protein was detected by Western analysis using the monoclonal 9A7 gamma anti-VDR antibody and a polyclonal rabbit anti-VDR antibody. For comparison, VDR levels were analyzed in cultures of normal human keratinocytes and the epithelial cell line MCF-7. Studies of the extraction procedures for VDR showed that at least 60% of Escherichia coli-expressed VDR added to the skin biopsy specimens was recovered. The VDR concentration in normal human adult skin was approximately 50 pg/microgram protein, and the concentrations of VDR in involved and uninvolved psoriatic skin were of the same order of magnitude. Using the 9A7 gamma anti-VDR antibody, the VDR (M(r) 53,000) was constantly present in lower amounts than a band of M(r) 80,000 in both skin specimens and keratinocyte cultures. This high-molecular-weight band is most likely a cross-reacting protein not related to VDR, because it was absent when using the polyclonal anti-VDR antibody.
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PMID:Normal levels of the vitamin D receptor and its message in psoriatic skin. 962 88

Calcitriol, via its receptor (VDR) is a main regulator of PTH secretion and parathyroid cell proliferation. Recently, marked overrepresentation of the polymorphic VDR alleles b, a, and T was found in patients with primary hyperparathyroidism (pHPT), which suggests pathogenic importance in the disease. Using the ribonuclease protection assay, relative VDR and PTH messenger ribonucleic acid (mRNA) levels of parathyroid adenomas from 42 patients with sporadic pHPT were related to these VDR polymorphisms. The tumors of patients homozygous for the b, a, or T alleles demonstrated significantly lower VDR and higher PTH mRNA levels than those exhibiting the BB, AA, or tt genotypes (P < 0.0001-0.02), whereas heterozygotes had intermediate values. A similar discrepancy was found when comparing the baT and non-baT haplotypes (0.042 +/- 0.005 vs. 0.064 +/- 0.004 for VDR; 34.4 +/- 3.7 vs. 21.6 +/- 2.2 for PTH; both P < 0.005). The lower VDR mRNA levels associated with the b, a, and T alleles may affect the calcitriol-mediated control of parathyroid function and thereby contribute to the development of sporadic pHPT.
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PMID:Vitamin D receptor (VDR) and parathyroid hormone messenger ribonucleic acid levels correspond to polymorphic VDR alleles in human parathyroid tumors. 966 91