Cooperation between BRCA1 and vitamin D is critical for histone acetylation of the p21waf1 promoter and for growth inhibition of breast cancer cells and cancer stem-like cells.

Pickholtz, Itay; Saadyan, Shira; Keshet, Gilmor I.; Wang, Victor S.; Cohen, Richard L.; Bouwman, Peter; Jonkers, Jos; Byers, Stephen W.; Papa, Moshe Z.; Yarden, Ronit I.

doi:10.18632/oncotarget.2582

Cited by 20 publications

(19 citation statements)

References 61 publications

(82 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Moreover, it intervenes in other mitogenic signaling pathways (e.g., ERK/mitogen-activated protein kinase pathway and c-myc) (344,480). In BRCA1-positive breast cancer cells, liganded VDR associates with BRCA1, and this complex occupies VDREs in the p21 promoter to enhance promoter acetylation and p21 expression, revealing a novel aspect of BRCA unrelated to DNA repair (360).…”

Section: In Vitro Antineoplastic Effects Of 125(oh) 2 Dmentioning

confidence: 99%

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

1,347

1,177

View full text Add to dashboard Cite

, [1,25(OH) 2 D 3 ] is the hormonally active form of vitamin D. The genomic mechanism of 1,25(OH) 2 D 3 action involves the direct binding of the 1,25(OH) 2 D 3 activated vitamin D receptor/retinoic X receptor (VDR/RXR) heterodimeric complex to specific DNA sequences. Numerous VDR co-regulatory proteins have been identified, and genome-wide studies have shown that the actions of 1,25(OH) 2 D 3 involve regulation of gene activity at a range of locations many kilobases from the transcription start site. The structure of the liganded VDR/RXR complex was recently characterized using cryoelectron microscopy, X-ray scattering, and hydrogen deuterium exchange. These recent technological advances will result in a more complete understanding of VDR coactivator interactions, thus facilitating cell and gene specific clinical applications. Although the identification of mechanisms mediating VDR-regulated transcription has been one focus of recent research in the field, other topics of fundamental importance include the identification and functional significance of proteins involved in the metabolism of vitamin D. CYP2R1 has been identified as the most important 25-hydroxylase, and a critical role for CYP24A1 in humans was noted in studies showing that inactivating mutations in CYP24A1 are a probable cause of idiopathic infantile hypercalcemia. In addition, studies using knockout and transgenic mice have provided new insight on the physiological role of vitamin D in classical target tissues as well as evidence of extraskeletal effects of 1,25(OH) 2 D 3 including inhibition of cancer progression, effects on the cardiovascular system, and immunomodulatory effects in certain autoimmune diseases. Some of the mechanistic findings in mouse models have also been observed in humans. The identification of similar pathways in humans could lead to the development of new therapies to prevent and treat disease.

show abstract

Section: In Vitro Antineoplastic Effects Of 125(oh) 2 Dmentioning

confidence: 99%

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

1,347

1,177

View full text Add to dashboard Cite

show abstract

“…96,97 In other epithelial tissues, close cooperation between VDR regulates BRCA1 mRNA and protein via transcriptional activation, again supporting a role in genomic surveillance. [98][99][100]…”

Section: Limitless Replicative Potentialmentioning

confidence: 99%

Vitamin D Receptor Signaling and Cancer

Campbell

Trump

2017

Endocrinology and Metabolism Clinics of North America

View full text Add to dashboard Cite

The primary biological action of the secosteroid hormone vitamin D (1,25(OH) 2 D 3 ) is to bind to the vitamin D receptor (NR1I1/VDR) and to regulate serum calcium levels. As a downstream consequence, the actions of the receptor control bone formation and maintenance. The first clinical manifestation of insufficient VDR endocrine signaling, rickets, was discovered by Daniel Whistler in the Netherlands in the 17th century; 300 years later, the VDR gene was cloned by Bert O'Malley and coworkers. 1 Between these dates, research into vitamin D was at the forefront of areas of public health, chemistry and biochemistry including the light catalyzed synthesis of vitamin D 3 by Adolf Windaus. For this work, he received the Nobel Prize in Chemistry (1928). Work in the 1960s and 1970s led to analyses of vitamin D endocrine metabolism and led to remarkable strides describing biochemical synthesis of 1,25(OH) 2 D 3 and the diverse biology in which VDR participates.The precursor of 1,25(OH) 2 D 3 , cholecalciferol or vitamin D 3 , is produced in the skin and converted in the liver to 25-hydroxyvitamin D 3 , (25(OH)D 3 ); circulating levels of 25(OH)D 3 serve as a useful index of vitamin D total body stores. A further hydroxylation occurs in the principally in the kidney at the carbon 1 position by 25-hydroxyvitamin D-1α-hydroxylase (encoded by CYP27B1) to produce the biologically active hormone, 1,25(OH) 2 D 3 . A second mitochondrial cytochrome P450 enzyme, the 24-hydroxylase (encoded by CYP24A1), can use both 25(OH)D and 1,25(OH) 2 D 3 as substrates, and is the first step in the inactivation pathway for these metabolites. Because of the direct role 1,25(OH) 2 D 3 plays in control of serum calcium levels, elevated levels of 1,25(OH) 2 D 3 block its synthesis and induce inactivation and accelerate catabolism 2 via induction of CYP24A1, in a classical negative feedback loop.This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). The first report that VDR actions could control cancer cell growth were discovered partly through serendipity, and partly through logical extension of other studies. Reports in the 1970s identified purified cell fractions that bound 1,25(OH) 2 D 3 with high affinity, 14 and encouraged investigators to begin to consider what were the molecular actions of the VDR in the classic tissues involved in calcium homeostasis, for example, skin, bone, intestine, and kidney. 15 In 1981, Kay Colston and coworkers 16 were first to demonstrate that 1α,25(OH) 2 D 3 at nanomolar concentrations inhibited human melanoma cell proliferation in vitro. That the workers used a cancer cell model was serendipitous; cancer cell models are more readily available to study in cell culture experiments than nonmalignant counterparts, and in this case 16 the cells chosen were available in an adjacent laboratory. Campbell and Trump In parallel, it was also known that retinoids, which are also small lipophilic molecules that target NRs, could drive cell differentiation, for exa...

show abstract

“…Another molecular mechanism of BRCA1-dependent growth inhibition of BC stem-like cells and BC cells was described by Pickholtz et al (2014). In this work it was demonstrated that BRCA1 in the presence of vitamin D binds to vitamin D responsive elements at the p21waf1 promoter, inducing the acetylation of histone H3 and H4 at this promoter that leads further to increased expression of p21waf1 followed by growth inhibition of both BC stem-like cells and BC cells.…”

Section: Role Of Brca1 In Bc Stem Cells (Bcscs) Developmentmentioning

confidence: 83%

Epigenetic regulation of BRCA1 expression and its role inbreast cancer stem cell development

Shestakova¹

2016

Turk J Biol

View full text Add to dashboard Cite

Recent reports also point to the important role of BRCA1 in cancer stem cell development, and particularly BC stem cell development. Due to the fact that the inhibition of BRCA1 function is related to the development of oncologic diseases, in particular BC and OC, and in some cases lung, pancreatic, gastric, and head and neck cancers, recent studies demonstrated the prognostic and predictive value of BRCA1 expression at the protein level for the course of the disease and sensitivity to platinum-based chemotherapy. In this review articles cited recently in the Pubmed system are analyzed. 2. BRCA1 protein structure and its role in homologous recombination-dependent DNA repair BRCA1 functioning as a tumor suppressor is mainly due to its participation in genome stability control that depends on its interaction with multiple associated proteins. The domain structure of the BRCA1 protein with its associated partners is presented in Figure 1. This figure is based on multiple articles and comprehensive reviews (

show abstract

Cooperation between BRCA1 and vitamin D is critical for histone acetylation of the p21waf1 promoter and for growth inhibition of breast cancer cells and cancer stem-like cells.

Cited by 20 publications

References 61 publications

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects

Vitamin D Receptor Signaling and Cancer

Epigenetic regulation of BRCA1 expression and its role inbreast cancer stem cell development

Contact Info

Product

Resources

About