Vitamin D-3 Receptor as a Target for Breast Cancer Prevention

Welsh, JoEllen; Wietzke, Jennifer A.; Zinser, Glendon M.; Byrne, Belinda; Smith, Kelly M.; Narvaez, Carmen J.

doi:10.1093/jn/133.7.2425s

Cited by 146 publications

(125 citation statements)

References 52 publications

Supporting

Mentioning

110

Contrasting

Unclassified

Order By: Relevance

“…49 Vitamin D is available in small amounts in foods such as fish, eggs and fortified dairy products. In addition, many multivitamins and supplements containing vitamin D are available.…”

Section: Basic Facts About Vitamin Dmentioning

confidence: 99%

Vitamin D and prostate cancer risk: a review of the epidemiological literature

Gupta

Lammersfeld

Trukova

et al. 2009

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

Prostate cancer is the most commonly diagnosed cancer in the United States. Prostate cells contain vitamin D receptors as well as enzymes necessary for vitamin D metabolism. Vitamin D metabolites have an antiproliferative and a pro-differentiating effect on prostate cancer cell lines in vitro and in vivo. As a result, there has been an emerging interest in the potential role of vitamin D in the etiology of prostate cancer. This review summarizes all available epidemiological literature on the association between dietary vitamin D, circulating levels of vitamin D and sunlight exposure in relation to prostate cancer risk. To place these studies in context, we also provide some background information on vitamin D, such as its dietary sources, metabolism, optimal levels, hypovitaminosis and relationship with the prostate.

show abstract

“…49 Vitamin D is available in small amounts in foods such as fish, eggs and fortified dairy products. In addition, many multivitamins and supplements containing vitamin D are available.…”

Section: Basic Facts About Vitamin Dmentioning

confidence: 99%

Vitamin D and prostate cancer risk: a review of the epidemiological literature

Gupta

Lammersfeld

Trukova

et al. 2009

Prostate Cancer Prostatic Dis

View full text Add to dashboard Cite

show abstract

“…The antiproliferative actions of vitamin D 3 in various cell models have been associated with induction of G 1 cell cycle arrest and/or induction of apoptosis (18,43,44), and we examined the extent to which MCF-12A cells displayed either of these responses. After 24-hour exposure to 1a,25(OH) 2 D 3 (100 nmol/L), there was a significant accumulation of cells in G 1 (62 F 4%; P < 0.05) compared with 43% in G 0 -G 1 in matched mid-exponentially proliferating control cells and a concomitant reduction in the proportion of cells in S and G 2 -M phase.…”

Section: à6mentioning

confidence: 99%

Altered Nuclear Receptor Corepressor Expression Attenuates Vitamin D Receptor Signaling in Breast Cancer Cells

Banwell¹,

MacCartney²,

Guy

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose:We hypothesized that deregulated corepressor actions, with associated histone deacetylation activity, epigenetically suppressed vitamin D receptor (VDR) responsiveness and drives resistance towards 1a,25-dihydroxyvitamin D 3 . Experimental Design: Profiling, transcriptional, and proliferation assays were undertaken in 1a,25(OH) 2 D 3 -sensitive MCF-12A nonmalignant breast epithelial cells, a panel of breast cancer cell lines, and a cohort of primary breast cancer tumors (n = 21). Results: Elevated NCoR1 mRNA levels correlated with suppressed regulation of VDR target genes and the ability of cells to undergo arrest in G 1 of the cell cycle. A similar increased ratio of corepressor mRNA to VDR occurred in matched primary tumor and normal cells, noticeably in estrogen receptor a^negative (n = 7) tumors. 1a,25(OH) 2 D 3 resistance in cancer cell lines was targeted by cotreatments with either 1a,25(OH) 2 D 3 or a metabolically stable analogue (RO-26-2198) in combination with either trichostatin A (TSA; histone deacetylation inhibitor) or 5-aza-2V-deoxycytidine (DNA methyltransferase inhibitor). Combinations of vitamin D 3 compounds with TSA restored VDR antiproliferative signaling (target gene regulation, cell cycle arrest, and antiproliferative effects in liquid culture) to levels which were indistinguishable from MCF-12A cells. Conclusions: Increased NCoR1 mRNA is a novel molecular lesion in breast cancer cells, which acts to suppress responsiveness of VDR target genes, resulting in 1a,25(OH) 2 D 3 resistance and seems to be particularly associated with estrogen receptor negativity.This lesion provides a novel molecular diagnostic and can be targeted by combinations of vitamin D 3 compounds and low doses of TSA.The nuclear receptor superfamily regulates diverse signals that are central to the formation and homeostasis of the mammary gland. The postgenomic description of the superfamily conjoined with profiling approaches (1) reveals that breast myoepithelial and epithelial cells express a rich cohort of nuclear receptors, many of which display overt nutrient-sensing capacity for micronutrients and macronutrients alongside the estrogen receptors (ERa and ERh; refs. 2 -6).Several of the diet-sensing nuclear receptors, such as the VDR, preferentially form heterodimers with retinoid X receptors whereas the ERs preferentially heterodimerize with one another. For the nuclear receptors to regulate transcriptional programs, these dimers must be contained as subunits in either large gene coactivator or corepressor complexes. In the absence of ligand, receptors exist in an apo state as part of large complexes (f2.0 MDa; ref. 7), associated with corepressors (e.g., NCoR1, NCoR2/SMRT, and TRIP15/Alien), and bound to response element sequences. These complexes actively recruit a range of enzymes that posttranslationally modify histone tails (e.g., histone deacetylases and methyltransferases) and thereby maintain a locally closed chromatin structure around response element sequences (8). Ligand binding induces a...

show abstract

“…25(OH)D is converted to 1,25-dihydroxyvitamin D [1,25(OH) 2 D], the biologically active form of vitamin D, in the liver and other tissues including breast. [18][19][20] Few studies have assessed the relationship between serum or plasma 25(OH)D and breast cancer risk. [21][22][23][24][25] Of 2 small hospitalbased case-control studies in predominantly postmenopausal women, one study found a significantly inverse association 23 whereas the other study revealed no association between plasma 25(OH)D and breast cancer risk.…”

mentioning

confidence: 99%

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Abbas

Chang‐Claude

Linseisen

2008

Intl Journal of Cancer

110

View full text Add to dashboard Cite

Laboratory and epidemiological data have linked vitamin D to breast cancer prevention. Beside dietary intake, endogenous production of vitamin D substantially contributes to a subject's vitamin D status. Most studies, however, have assessed dietary intake only. Although differential effects of vitamin D on premenopausal and postmenopausal breast cancer have been discussed, this is the first study to investigate the association of plasma 25-hydroxyvitamin D [25(OH)D], as indicator of the overall vitamin D status, with breast cancer risk with restriction to premenopausal women only. We used data of a population-based case-control study comprising 289 cases and 595 matched controls. Information on sociodemographic and breast cancer risk factors was collected by questionnaire and plasma 25(OH)D was measured by enzyme immunoassay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression. We observed a significant inverse association between breast cancer risk and plasma 25(OH)D concentrations. Compared with the lowest category (<30 nmol/L), the ORs (95% CI) for the upper categories [18][19][20] Few studies have assessed the relationship between serum or plasma 25(OH)D and breast cancer risk. [21][22][23][24][25] Of 2 small hospitalbased case-control studies in predominantly postmenopausal women, one study found a significantly inverse association 23 whereas the other study revealed no association between plasma 25(OH)D and breast cancer risk. 25 To date, 2 studies assessed the association of vitamin D metabolites with breast cancer risk with restriction to postmenopausal women only. 21,22 A study nested in the prostate, lung, colorectal and ovarian cancer screening trial reported no association between both higher plasma 25(OH)D and 1,25(OH) 2 D concentration and breast cancer risk. 22 However, a strong statistically significant inverse association between postmenopausal breast cancer risk and serum 25(OH)D was found in a large case-control study. 21 A case-control study nested in the Nurses' Health Study (NHS) is the only study that so far reported results stratified by menopausal status. 24 The authors reported a nonsignificant decrease in breast cancer risk with both higher plasma 25(OH)D and 1,25(OH) 2 D concentration for overall breast cancer risk. Stratification by menopausal status suggested an inverse association for postmenopausal women only, however power was low for their analysis in premenopausal women and risk estimates were not presented. As reviewed recently, prospective studies on dietary intake of vitamin D suggest a more pronounced effect for premenopausal breast cancer risk. 26 Furthermore, we recently reported a significant inverse association of dietary vitamin D with premenopausal breast cancer risk in the present study population. 13 To our knowledge, no study so far assessed the association of plasma 25(OH)D with restriction to premenopausal breast cancer only. Following our previous report on the association between postmenopausal breast canc...

show abstract

Vitamin D-3 Receptor as a Target for Breast Cancer Prevention

Cited by 146 publications

References 52 publications

Vitamin D and prostate cancer risk: a review of the epidemiological literature

Vitamin D and prostate cancer risk: a review of the epidemiological literature

Altered Nuclear Receptor Corepressor Expression Attenuates Vitamin D Receptor Signaling in Breast Cancer Cells

Plasma 25‐hydroxyvitamin D and premenopausal breast cancer risk in a German case‐control study

Contact Info

Product

Resources

About