Differential expression and regulation of vitamin D hydroxylases and inflammatory genes in prostate stroma and epithelium by 1,25-dihydroxyvitamin D in men with prostate cancer and an in vitro model

Giangreco, Angeline A.; Dambal, Shweta; Wagner, David G.; Kwast, Theodorus H. van der; Vieth, Reinhold; Prins, Gail S.; Nonn, Larisa

doi:10.1016/j.jsbmb.2014.10.004

Cited by 44 publications

(51 citation statements)

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“…In addition, nuclear factor kappa-lightchain-enhancer of activated B cells (NF-B) signaling, a major mediator of the immune response, is inhibited in various cancers by 1,25(OH) 2 D 3 by acting on different members of this pathway (304, 455) (FIGURE 7). A suppressed production of inflammatory cytokines, such as interleukin (IL)-1, IL-6, IL-8, IL-17, and TNF-␣ is consistently demonstrated in in vitro and in vivo cancer models (5,162,240,330) (FIGURE 7). In a preclinical SMAD3 knockout model of colitis and colon cancer, Meeker et al (304) showed that a high vitamin D diet decreases NF-B activation in colonic epithelial cells, which is reflected by decreased inflammatory cell infiltrates and reduced expression of proinflammatory cytokines during initiation of carcinogenesis (304).…”

Section: D) Effects On Inflammation In Cancermentioning

confidence: 95%

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

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

1,473

1,234

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, [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.

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Section: D) Effects On Inflammation In Cancermentioning

confidence: 95%

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

Christakos

Dhawan

Verstuyf

et al. 2016

Physiological Reviews

1,473

1,234

View full text Add to dashboard Cite

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“…Primary human stromal (PrS) cells were isolated from radical prostatectomy tissue from PCa patients at the University of Illinois at Chicago Medical Center according to an Institutional Review Board-approved protocol previously described [17]. Briefly, fresh tissue from the peripheral zone was excised with a 5 mm punch from transverse sections of radical prostatectomy specimens by a pathologist.…”

Section: Methodsmentioning

confidence: 99%

“…Prostate stroma from benign areas was collected by LCM as described earlier by Nonn and colleagues [17, 19, 21]. Briefly, two 8 μM formalin-fixed paraffin-embedded sections from each prostatectomy specimen were mounted on RNase-free PEN slides (Leica, Buffalo Grove, IL).…”

Section: Methodsmentioning

confidence: 99%

“…Whereas, the role of other stromal steroid hormones and their receptors, such as androgen and estrogen, in regulating stromal-epithelial interactions in the prostate are well-studied [15], there are limited studies on vitamin D in the prostate stroma. Our lab recently showed that primary prostate stromal cells (PrS) and patient stromal tissues have a functional vitamin D signaling axis and that the stromal cells contribute to the anti-inflammatory effects of 1,25(OH) 2 D in primary prostate epithelial cells [17]. …”

Section: Introductionmentioning

confidence: 99%

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microRNAs and DICER1 are regulated by 1,25-dihydroxyvitamin D in prostate stroma

Dambal

Giangreco

Acosta

et al. 2017

The Journal of Steroid Biochemistry and Molecular Biology

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Vitamin D deficiency increases the risk of lethal prostate adenocarcinomas (PCa) and the majority of older men are deficient. Although PCa arises from the epithelium, the surrounding stroma has hormonal regulatory control over the epithelium and contributes to carcinogenesis. Herein, we describe regulation of microRNAs (miRs) by the active hormone dihydroxyvitamin D (1,25(OH)2D) in human prostate stroma. 1,25(OH)2D binds the vitamin D receptor (VDR) transcription factor to regulate gene expression, including miRs, which have emerged as potent regulators of protein expression. 1,25(OH)2D -regulated miRs were identified by profiling in primary human prostatic stromal cells (PrS) and three miRs, miR-126-3p, miR 154-5p and miR-21-5p were subsequently validated in laser-capture micro-dissected prostate stromal tissue from a vitamin D3 clinical trial (N=45). Regulation of these miRs by 1,25(OH)2D was VDR-dependent. Network analysis of known and putative mRNA targets of these miRs was enriched with cancer and inflammation pathways, consistent with known roles of stroma and of vitamin D in carcinogenesis. Expression of the miR processing ribonuclease, DICER1, positively correlated with vitamin D metabolite levels in the clinical trial specimens. High epithelial/stromal ratios of DICER1 were significantly associated biochemical recurrence (OR 3.1, p=0.03) in a tissue microarray of 170 matched PCa patients. In summary, these results underscore the role of the prostate stroma in regulating responses to the hormone 1,25(OH)2D and identified miRs and DICER1 as being regulated in human prostate stroma. Regulation of stromal DICER1 by 1,25(OH)2D may also have clinical relevance in protection against aggressive PCa.

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“…CYP27B1 expression can be inhibited also by the growth factor independent 1, which represses CYP27B1 transcription by binding to a repressive region in the promoter and recruiting co-repressors with histone deacetylase activity (Dwivedi et al, 2005). A recent study, comparing prostate epithelial and stromal cells from prostate cancer patients, found higher levels of CYP27B1, CYP2R1, and CYP24A1 both in the benign and cancerous epithelia compared with the surrounding stroma (Giangreco et al, 2015).…”

Section: -Hydroxyvitamin D 3 1-alpha Hydroxylase (Cyp27b1) In Cancermentioning

confidence: 99%