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Vdr ppar cancer vitamin d

Borja Bandera Merchan, Francisco José Tinahones, Manuel Macías-González
The PPAR nuclear receptor family has acquired great relevance in the last decade, which is formed by three different isoforms (PPARα, PPARβ/δ, and PPAR ϒ). Those nuclear receptors are members of the steroid receptor superfamily which take part in essential metabolic and life-sustaining actions. Specifically, PPARG has been implicated in the regulation of processes concerning metabolism, inflammation, atherosclerosis, cell differentiation, and proliferation. Thus, a considerable amount of literature has emerged in the last ten years linking PPARG signalling with metabolic conditions such as obesity and diabetes, cardiovascular disease, and, more recently, cancer...
2016: PPAR Research
Carl E Wagner, Peter W Jurutka, Pamela A Marshall, Michael C Heck
Since the isolation and identification of the retinoid X receptor (RXR) as a member of the nuclear receptor (NR) superfamily in 1990, its analysis has ushered in a new understanding of physiological regulation by nuclear receptors, and novel methods to identify other unknown and orphan receptors. Expression of one or more of the three isoforms of RXR-α, β, and γ-can be found in every human cell type. Biologically, RXR plays a critical role through its ability to partner with other nuclear receptors. RXR is able to regulate nutrient metabolism by forming "permissive" heterodimers with peroxisome proliferator-activated receptor (PPAR), liver-X-receptor (LXR), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstane receptor (CAR), which function when ligands are bound to one or both of the heterodimer partners...
2017: Current Topics in Medicinal Chemistry
Robert C Baxter
In addition to its actions outside the cell, cellular uptake and nuclear import of insulin-like growth factor binding protein-3 (IGFBP-3) has been recognized for almost two decades, but knowledge of its nuclear actions has been slow to emerge. IGFBP-3 has a functional nuclear localization signal and interacts with the nuclear transport protein importin-β. Within the nucleus IGFBP-3 appears to have a role in transcriptional regulation. It can bind to the nuclear receptor, retinoid X receptor-α and several of its dimerization partners, including retinoic acid receptor, vitamin D receptor (VDR), and peroxisome proliferator-activated receptor-γ (PPARγ)...
September 10, 2015: Gene
Satoru Matsuda, Yasuko Kitagishi
Peroxisome proliferator-activated receptors (PPARs) are members of the superfamily of nuclear hormone receptors, which respond to specific ligands such as polyunsaturated fatty acids by altering gene expression. Three subtypes of this receptor have been discovered, each evolving to achieve different biological functions. Like other nuclear receptors, the transcriptional activity of PPARs is affected not only by ligand-stimulation, but also by cross-talk with other molecules. For example, both PPARs and the RXRs are ligand-activated transcription factors that coordinately regulate gene expression...
2013: Cancers
Kevin C Knower, Ashwini L Chand, Natalie Eriksson, Kiyoshi Takagi, Yasuhiro Miki, Hironobu Sasano, Jane E Visvader, Geoffrey J Lindeman, John W Funder, Peter J Fuller, Evan R Simpson, Wayne D Tilley, Peter J Leedman, J Dinny Graham, George E O Muscat, Christine L Clarke, Colin D Clyne
The interaction between breast tumor epithelial and stromal cells is vital for initial and recurrent tumor growth. While breast cancer-associated stromal cells provide a favorable environment for proliferation and metastasis, the molecular mechanisms contributing to this process are not fully understood. Nuclear receptors (NRs) are intracellular transcription factors that directly regulate gene expression. Little is known about the status of NRs in cancer-associated stroma. Nuclear Receptor Low-Density Taqman Arrays were used to compare the gene expression profiles of all 48 NR family members in a collection of primary cultured cancer-associated fibroblasts (CAFs) obtained from estrogen receptor (ER)α positive breast cancers (n = 9) and normal breast adipose fibroblasts (NAFs) (n = 7)...
November 2013: Breast Cancer Research and Treatment
A Hossein-Nezhad, K Mirzaei, S A Keshavarz, H Ansar, S Saboori, A Tootee
AIM: The underlying molecular mechanisms of the role obesity plays in increasing the risk of cancer are not well illuminated. Several mechanisms are proposed for vitamin D as an anti-cancer agent in various malignancies which may be attributed to both its both its anti-inflammatory characteristics as well as its mediatory role in cellular energy homeostasis. This study evaluates the expression of PBMCs' genes which are involved in cellular energy homeostasis such as VDR, PPARγ, PGC1a and UCP2...
June 2013: Minerva Medica
Nina Ditsch, Doris Mayr, Miriam Lenhard, Carolin Strauss, Andrea Vodermaier, Julia Gallwas, Doris Stoeckl, Monika Graeser, Tobias Weissenbacher, Klaus Friese, Udo Jeschke
Non-steroidal nuclear receptors play a major role in breast cancer development. A correlation among, and possible prognostic function of, the members of the nuclear receptor superfamily has been discussed controversially over the years. Hence, we conducted a quantification of the different expression levels of the thyroid receptor (TR), retinoid X receptor (RXR), peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR) in malignant breast tumour tissue samples. Patients diagnosed and treated for breast cancer between 1990 and 2000 were included...
October 2012: Oncology Letters
Wei-Lin Winnie Wang, Joellen Welsh, Martin Tenniswood
Previous studies from our laboratory have shown that testosterone (T) and 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) co-operate to inhibit cell proliferation and induce significant changes in gene expression and differentiation in LNCaP cells. The data presented here demonstrate that the two agents alter fatty acid metabolism, and accumulation of neutral lipid. Concurrent genome wide analysis of mRNA and miRNA in LNCaP cells reveals an extensive transcription regulatory network modulated by T and 1,25(OH)2D3. This involves not only androgen receptor (AR)- and vitamin D receptor (VDR)-mediated transcription, but also transcription factors E2F1- and c-Myc-dependent transcription...
July 2013: Journal of Steroid Biochemistry and Molecular Biology
Fatouma Alimirah, Xinjian Peng, Liang Yuan, Rajeshwari R Mehta, Andreas von Knethen, Divaker Choubey, Rajendra G Mehta
Heterodimerization and cross-talk between nuclear hormone receptors often occurs. For example, estrogen receptor alpha (ERα) physically binds to peroxisome proliferator-activated receptor gamma (PPARγ) and inhibits its transcriptional activity. The interaction between PPARγ and the vitamin D receptor (VDR) however, is unknown. Here, we elucidate the molecular mechanisms linking PPARγ and VDR signaling, and for the first time we show that PPARγ physically associates with VDR in human breast cancer cells...
November 15, 2012: Experimental Cell Research
Richard G Moore, Thilo S Lange, Katina Robinson, Kyu K Kim, Alper Uzun, Timothy C Horan, Nada Kawar, Naohiro Yano, Sharon R Chu, Quanfu Mao, Laurent Brard, Monique E DePaepe, James F Padbury, Leggy A Arnold, Alexander Brodsky, Tun-Li Shen, Rakesh K Singh
BACKGROUND: Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING: Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3) xenografts in nude mice and a syngenic rat ovarian cancer model...
2012: PloS One
Pit Sertznig, Markus Seifert, Wolfgang Tilgen, Jörg Reichrath
We have investigated expression of vitamin D receptor (VDR) and peroxisome proliferator-activated receptors (PPAR)alpha, delta, gamma in primary cultured normal melanocytes (NHM), melanoma cell lines (MeWo, SK-Mel-5, SK-Mel-25, SK-Mel-28), a cutaneous squamous cell carcinoma cell line (SCL-1) and an immortalized sebocyte cell line (SZ95). LNCaP prostate cancer cells, MCF-7 breast cancer cells and embryonic kidney cells (HEK-293) were used as controls. VDR and PPAR mRNA were detected, quantitated and compared in these cell lines using real-time quantitative polymerase chain reaction (RTqPCR)...
July 2009: Dermato-endocrinology
Pit Sertznig, Markus Seifert, Wolfgang Tilgen, Jörg Reichrath
Peroxisome proliferator-activated receptor (PPAR) and vitamin D receptor (VDR) signaling pathways regulate a multitude of genes that are of importance for a multitude of cellular functions including cell proliferation, cell differentiation, immune responses and apoptosis. Ligands and other agents influencing the PPAR and VDR signaling pathways have been shown to reveal chemopreventive potential by mediating tumor suppressive activities in a variety of human cancers. Use of these compounds may represent a potential novel strategy to prevent melanoma pathogenesis and to inhibit melanoma progression...
July 2010: Journal of Steroid Biochemistry and Molecular Biology
Jiyoung Ahn, Demetrius Albanes, Sonja I Berndt, Ulrike Peters, Nilanjan Chatterjee, Neal D Freedman, Christian C Abnet, Wen-Yi Huang, Adam S Kibel, E David Crawford, Stephanie J Weinstein, Stephen J Chanock, Arthur Schatzkin, Richard B Hayes
We systematically investigated the association of 48 SNPS in four vitamin D metabolizing genes [CYP27A1, GC, CYP27B1 and CYP24A1] with serum 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] levels and the association of these SNPS and an additional 164 SNPS in eight downstream mediators of vitamin D signaling [VDR, RXRA, RXRB, PPAR, NCOA1, NCOA2, NCOA3 and SMAD3] with prostate cancer risk in the 749 incident prostate cancer cases and 781 controls of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial...
May 2009: Carcinogenesis
S Asad Abedin, James L Thorne, Sebastiano Battaglia, Orla Maguire, Laura B Hornung, Alan P Doherty, Ian G Mills, Moray J Campbell
Increasingly invasive bladder cancer cells lines displayed insensitivity toward a panel of dietary-derived ligands for members of the nuclear receptor superfamily. Insensitivity was defined through altered gene regulatory actions and cell proliferation and reflected both reduced receptor expression and elevated nuclear receptor corepressor 1 (NCOR1) expression. Stable overexpression of NCOR1 in sensitive cells (RT4) resulted in a panel of clones that recapitulated the resistant phenotype in terms of gene regulatory actions and proliferative responses toward ligand...
March 2009: Carcinogenesis
Markus Schwab, Veerle Reynders, Stefan Loitsch, Dieter Steinhilber, Jürgen Stein, Oliver Schröder
BACKGROUND: NF kappa B plays a major role in the control of immune responses and inflammation. Recently, butyrate has not only been demonstrated to suppress NF kappa B activation in colorectal cancer cells, but also to modulate the activity and expression of the Peroxisome-Proliferator-Activated-Receptor gamma (PPAR gamma) and the vitamin D receptor (VDR). Therefore, we investigated a putative involvement of both receptors in butyrate-mediated inhibition of inducible NF kappa B signalling...
July 2007: Molecular Immunology
Thomas W Dunlop, Sami Väisänen, Christian Frank, Ferdinand Molnár, Lasse Sinkkonen, Carsten Carlberg
Peroxisome proliferator-activated receptor (PPAR) delta is the most widely expressed member of the PPAR family of nuclear receptor fatty acid sensors. Real-time PCR analysis of breast and prostate cancer cell lines demonstrated that PPARdelta expression was increased 1.5 to 3.2-fold after three hours stimulation with the natural vitamin D receptor (VDR) agonist, 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3). In silico analysis of the 20 kb of the human PPARdelta promoter revealed a DR3-type 1alpha,25(OH)2D3 response element approximately 350 bp upstream of the transcription start site, which was able to bind VDR-retinoid X receptor (RXR) heterodimers and mediate a 1alpha,25(OH)2D3-dependent upregulation of reporter gene activity...
June 3, 2005: Journal of Molecular Biology
Donna M Peehl, David Feldman
A number of hormonal ligands and/or the nuclear receptors that mediate their actions have been targeted for prostate cancer therapy. Androgens, the ligands for the androgen receptor (AR), are critical for the growth of prostate cancer. Inhibition of androgen production has been the mainstay of treatment for advanced prostate cancer for decades. Other more recently tested targets include retinoid receptors (RAR and RXR), glucocorticoid receptors (GR), estrogen receptors (ER) and peroxisome proliferator-activated receptors (PPAR)...
November 2004: Journal of Steroid Biochemistry and Molecular Biology
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