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Friedrich, Michael; Axt-Fliedner, R; Villena-Heinsen, C; Tilgen, Wolfgang; Schmidt, Werner; Reichrath, Jörg

doi:10.1023/a:1021343825552

Cited by 58 publications

(19 citation statements)

References 25 publications

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“…Some studies have demonstrated that the VDR protein is expressed in samples from normal breast tissues and also in breast cancer biopsy specimens [14,15,24,25]. Our results have shown that the VDR is expressed in carcinomas.…”

Section: Discussionsupporting

confidence: 73%

Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions

et al. 2010

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BackgroundBreast cancer is a heterogeneous disease associated with different patient prognosis and responses to therapy. Vitamin D has been emerging as a potential treatment for cancer, as it has been demonstrated that it modulates proliferation, apoptosis, invasion and metastasis, among others. It acts mostly through the Vitamin D receptor (VDR) and the synthesis and degradation of this hormone are regulated by the enzymes CYP27B1 and CYP24A1, respectively. We aimed to study the expression of these three proteins by immunohistochemistry in a series of breast lesions.MethodsWe have used a cohort comprising normal breast, benign mammary lesions, carcinomas in situ and invasive carcinomas and assessed the expression of the VDR, CYP27B1 and CYP24A1 by immunohistochemistry.ResultsThe results that we have obtained show that all proteins are expressed in the various breast tissues, although at different amounts. The VDR was frequently expressed in benign lesions (93.5%) and its levels of expression were diminished in invasive tumours (56.2%). Additionally, the VDR was strongly associated with the oestrogen receptor positivity in breast carcinomas. CYP27B1 expression is slightly lower in invasive carcinomas (44.6%) than in benign lesions (55.8%). In contrast, CYP24A1 expression was augmented in carcinomas (56.0% in in situ and 53.7% in invasive carcinomas) when compared with that in benign lesions (19.0%).ConclusionsFrom this study, we conclude that there is a deregulation of the Vitamin D signalling and metabolic pathways in breast cancer, favouring tumour progression. Thus, during mammary malignant transformation, tumour cells lose their ability to synthesize the active form of Vitamin D and respond to VDR-mediated Vitamin D effects, while increasing their ability to degrade this hormone.

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Section: Discussionsupporting

confidence: 73%

Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions

et al. 2010

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“…In contrast to numerous studies on circulating vitamin D biomarkers and breast cancer, there are few studies on VDR expression in breast tumor tissues. In an earlier study of 228 breast cancer patients, VDR expression was not associated with any histopathological indicators, such as ER and Ki-67 status (20). Moreover, previous studies have shown VDR expression as a prognostic marker for prostate and lung cancer (21, 22), which has remained understudied in breast cancer.…”

Section: Introductionmentioning

confidence: 95%

Tumor Expression of Vitamin D Receptor and Breast Cancer Histopathological Characteristics and Prognosis

Alazhri

Zhang

Bshara

et al. 2017

Clinical Cancer Research

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Purpose Our previous work has shown low serum 25-hydroxyvitamin D concentrations in association with aggressive breast cancer subtypes. Vitamin D receptor (VDR) is central for vitamin D-mediated transcription regulation. Few studies have examined breast VDR expression with tumor characteristics or patient survival. Experimental Design VDR expression in breast tumor tissue microarrays was determined by immunohistochemistry in 1,114 female patients as low, moderate and strong expression based on an immunoreactive score, and examined with histopathological tumor characteristics and survival outcomes including progression free survival, breast cancer specific survival, and overall survival. Results A majority (58%) of breast tumors showed moderate or strong VDR expression. VDR expression was inversely related to aggressive tumor characteristics, including large tumor size, hormonal receptor (HR) negativity, and triple-negative subtype (p<0.05). In addition, VDR expression was also inversely related to Ki-67 expression among patients older than 50 years. Nevertheless, VDR expression was not associated with any patient survival outcomes examined. Conclusions In a large patient population, VDR expression is inversely associated with more aggressive breast cancer, but not with breast cancer survival outcomes. The present findings of VDR expression are consistent with our previous results of circulating vitamin D biomarkers, which provide two converging lines of evidence supporting the putative benefits of vitamin D against aggressive breast cancer. Because of the observational nature of our analyses, future studies are warranted to establish the causality of the reported associations.

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“…Reports suggest that down-regulation of RAR␣ during tumor progression coincides with loss of response to RAR ligand (33), and the loss of RAR␤ is commonly observed at the early stage of tumorigenesis in multiple cancers (3). Conversely, every RXR isotype is overexpressed in 66% of breast ductal carcinomas in in situ lesions (8), and in particular RXR␣ up-regulation is associated with malignant transformation (34). Collectively, these data indicate that activation of RXR/RXR homodimer may require exogenous RXR-ligand and high RXR expression, and the aberrant expression profile of RAR and RXR in tumors may provide an advantage for RXR-ligand-induced cancer therapy.…”

Section: P21mentioning

confidence: 99%

p21WAF1/CIP1 Is a Common Transcriptional Target of Retinoid Receptors

Tanaka

Suh

et al. 2007

Journal of Biological Chemistry

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The divergent response and the molecular mechanisms underlying the anti-cancer effects of retinoid X receptor (RXR) ligand (rexinoid) therapy are poorly understood. This study demonstrates that ligand-activated RXR homodimer facilitated G 1 arrest by up-regulation of p21 in vitro and in vivo but failed to induce G 1 arrest when p21 expression was blocked by p21 small interfering RNA. RXR ligand-dependent p21 up-regulation was transcriptionally controlled through the direct binding of RXR homodimers to two consecutive retinoid X response elements in the p21 promoter. Structural overlap of a retinoic acid response element with these retinoid X response elements led to a high affinity binding of retinoic acid receptor/RXR heterodimer to the retinoic acid response element, resulting in the prevention of RXR ligand-mediated p21 transactivation. These data show that p21 is a potential and novel molecular target for RXR ligandmediated anti-cancer therapy and that the expression level of retinoic acid receptor and RXR in tumors may be crucial to induce p21-mediated cell growth arrest in RXR ligand therapy.Retinoids are natural and synthetic vitamin A derivatives that regulate a multitude of biological processes in mammalian cells, including metabolism, development, cell proliferation, differentiation, and carcinogenesis (1). Carcinogen exposure causes squamous metaplasia of tracheal and other epithelia, and administration of vitamin A prevents tumor formation (2). Retinoids are clinically used to target selected human cancers (3,27). The actions of retinoids are mediated by two distinct classes of retinoid receptors, retinoic acid receptors (RAR␣, -␤, and -␥) 3 and retinoid X receptors (RXR␣, ␤, and ␥), which require all-trans-retinoic acid and 9-cis-retinoic acid, respectively, for transcriptional activation. RXR is a combinatorial partner in the nuclear receptor family that forms homo-or heterodimers with a variety of hormone and orphan receptors, including RAR, vitamin D receptor, thyroid hormone receptor (TR), peroxisome proliferator-activated receptor (PPAR), chicken ovalbumin upstream promoter transcription factor (COUP-TF), and other receptors (4). The dimeric receptors bind to specific DNA response element of target genes, and this DNA binding specificity is determined by the number of spacer nucleotides present between the two direct repeats of the canonical binding sequence AGGTCA (5). For instance, RAR and RXR heterodimer binds to retinoic acid response element (RARE) that contains two or five spacers (DR2 or -5), and RXR homodimer binds to retinoid X response element (RXRE) in which the half-sites are separated by a single nucleotide (DR1) (5). Direct binding of ligands to the receptors is required for transcriptional activation, and in the absence of ligands, this activation is blocked by binding of specific repressors to the receptors (6). Ligand binding triggers a release of the repressors from the complex and promotes interaction with co-activator complexes that forms a bridge between the nuclear recepto...

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Untitled

Cited by 58 publications

References 25 publications

Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions

Alterations in Vitamin D signalling and metabolic pathways in breast cancer progression: a study of VDR, CYP27B1 and CYP24A1 expression in benign and malignant breast lesions Vitamin D pathways unbalanced in breast lesions

Tumor Expression of Vitamin D Receptor and Breast Cancer Histopathological Characteristics and Prognosis

p21WAF1/CIP1 Is a Common Transcriptional Target of Retinoid Receptors

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