Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

Marra, Francesco La; Stinco, Giuseppe; Buligan, Cinzia; Chiriacò, Giovanni; Serraino, Diego; Loreto, Carla Di; Cauci, Sabina

doi:10.20892/j.issn.2095-3941.2017.0020

Cited by 16 publications

(15 citation statements)

References 57 publications

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“…Of note is that its decreased expression correlates with advanced melanoma staging, progression and decreased overall patient survival and disease-free survival time [ 45 , 46 ]. Accordingly, VDR polymorphism [ 41 , 42 , 72 ] and decreased levels of 25(OH)D 3 in the serum [ 33 , 86 ] positively correlate with melanoma prevalence and poor prognosis.…”

Section: Discussionmentioning

confidence: 99%

“…The anti-melanoma activity of vitamin D derivatives have been reported previously [ 35 , 36 , 37 , 38 , 39 , 40 ]. In addition, the presence of specific polymorphisms of VDR [ 41 , 42 , 43 ] or a decreased expression of VDR , CYP27B1 , CYP24A1 and defects in vitamin D signaling are linked to more advanced stages of melanoma or poorer prognosis [ 44 , 45 , 46 , 47 , 48 ]. Furthermore, proper supplementation with vitamin D is believed to be an important factor in cancer prevention [ 47 , 49 , 50 , 51 ].…”

Section: Introductionmentioning

confidence: 99%

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Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

Wasiewicz

Piotrowska

Wierzbicka

et al. 2018

IJMS

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Vitamin D is a precursor for secosteroidal hormones, which demonstrate pleiotropic biological activities, including the regulation of growth and the differentiation of normal and malignant cells. Our previous studies have indicated that the inhibition of melanoma proliferation by a short side-chain, low calcemic analog of vitamin D—21(OH)pD is not fully dependent on the expression of vitamin D receptor (VDR). We have examined the effects of classic vitamin D metabolites, 1,25(OH)2D3 and 25(OH)D3, and two low calcemic vitamin D analogs, (21(OH)pD and calcipotriol), on proliferation, mRNA expression and vitamin D receptor (VDR) translocation in three human melanoma cell lines: WM98, A375 and SK-MEL-188b (subline b of SK-MEL-188, which lost responsiveness to 1,25(OH)2D3 and became VDR−/−CYP27B1−/−). All tested compounds efficiently inhibited the proliferation of WM98 and A375 melanoma cells except SK-MEL-188b, in which only the short side-chain vitamin D analog—21(OH)pD was effective. Overall, 21(OH)pD was the most potent compound in all three melanoma cell lines in the study. The lack of responsiveness of SK-MEL-188b to 1,25(OH)2D3, 25(OH)D3 and calcipotriol is explained by a lack of characteristic transcripts for the VDR, its splicing variants as well as for vitamin D-activating enzyme CYP27B1. On the other hand, the expression of VDR and its splicing variants and other vitamin D related genes (RXR, PDIA3, CYP3A4, CYP2R1, CYP27B1, CYP24A1 and CYP11A1) was detected in WM98 and A375 melanomas with the transcript levels being modulated by vitamin D analogs. The expression of VDR isoforms in WM98 cells was stimulated strongly by calcipotriol. The antiproliferative activities of 21(OH)pD appear not to require VDR translocation to the nucleus, which explains the high efficacy of this noncalcemic pregnacalciferol analog in SK-MEL-188b melanoma, that is, VDR−/−. Therefore, we propose that 21(OH)pD is a good candidate for melanoma therapy, although the mechanism of its action remains to be defined.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

Wasiewicz

Piotrowska

Wierzbicka

et al. 2018

IJMS

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“…VDR cistrome analyses suggested that altered expression of VDR in colon cancer changes actions of VDR, thus affecting patient outcome 58 . A recent study showed that VDR genetic traits can modulate VDR protein expression in excised human melanoma tissues, which might have implications for effects of vitamin D activity on melanoma cells 59 .…”

Section: Discussionmentioning

confidence: 99%

BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Cauci

Maione

Buligan

et al. 2017

Cancer Biology & Medicine

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Objective: To investigate whether vitamin D receptor gene (VDR) BsmI-rs1544410 and FokI-rs2228570 polymorphisms, smoking duration, and body mass index (BMI) are risk factors for cutaneous melanoma, especially metastatic melanoma. Methods: We studied 120 cutaneous melanoma cases [68 stage I and II non-metastatic melanoma (NMetM) patients, plus 52 Stage III and IV metastatic melanoma (MetM) patients], and 120 matching healthy controls from northeast Italy. VDR polymorphisms were measured by restriction fragment length polymorphism analysis. Absence or presence of BsmI and FokI restriction sites was denoted by " B” and " F” or by " b” and " f,” respectively. Results: VDR-BsmI bb genotype was more frequent among MetM (32.7%) than among NMetM cases (13.2%), with odds ratio (OR)=3.18. Comparison of all melanoma patients vs healthy controls showed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.43); ≥20 years of smoking combined with bb (OR=4.78), Bb+bb (OR=2.30), Ff (OR=3.04), and Ff+ff (OR=3.08); obesity (BMI>30 kg/m2) alone (OR=3.54); and obesity combined with Bb+bb (OR=3.52), Ff (OR=4.78), and Ff+ff (OR=6.56). Comparison of MetM vs NMetM patients revealed that the following biomarkers were at risk: ≥20 years of smoking (OR=2.39), ≥20 years of smoking combined with bb (OR=5.13), Bb+bb (OR=3.07), and Ff+ff (OR=2.66); and obesity combined with Bb+bb (OR=5.27), Ff (OR=6.28), and Ff+ff (OR=9.18). Triple combination of ≥20 years of smoking, obesity, and Bb+bb yielded OR=9.65 for melanoma patients vs healthy controls and OR=12.2 for MetM vs. NMetM patients. Conclusions: Risk factors for cutaneous MetM include two VDR polymorphisms combined with smoking duration and obesity. Results suggest gene-environment implications in melanoma susceptibility and severity. Future studies in larger cohorts and in subjects with different genetic background are warranted to extend our findings.

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“…While a functional role of VDR gene polymorphisms has not yet been established, the association between Apa-I gene variant and MetS observed in the present study could be assumed to be linked to disturbed VDR gene expression [ 33 ]. The Apa-I polymorphism is located at the 3′ untranslated region (3′ UTR) of the VDR gene, which has been recognized as being involved in the modulation of gene expression, especially through the regulation of mRNA stability and efficiency of protein translation [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Apa-I polymorphism in VDR gene is related to metabolic syndrome in polycystic ovary syndrome: a cross-sectional study

Santos

Lecke

Spritzer

2018

Reprod Biol Endocrinol

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BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder determined by polygenic traits as well as environmental factors. Lower vitamin D levels have been detected in PCOS women and related to hormone and metabolic disturbances. Vitamin D acts in tissues through the vitamin D receptor (VDR). VDR gene variants have been associated with worse metabolic profile in the general population. We investigated the genotype and haplotype distribution of the Bsm-I (rs1544410), Apa-I (rs7975232), and Taq-I (rs731236) VDR gene polymorphisms in PCOS and non-hirsute women from southern Brazil. We further investigated the associations of these gene variants and their haplotypes with PCOS, vitamin D levels, and metabolic abnormalities, including the metabolic syndrome (MetS).MethodsA group of 191 women with PCOS (Rotterdam criteria) and 100 non-hirsute controls with regular ovulatory cycles were genotyped for all polymorphisms by real-time PCR, with allelic discrimination assays. MetS and the cutoffs for its isolated components were defined in accordance with the Joint Scientific Statement.ResultsWomen with PCOS were younger and had significantly higher BMI and total testosterone levels than controls (p < 0.05). The frequency of MetS in PCOS and controls was 26.5% and 4.8% respectively. The CC genotype of Apa-I entailed higher risk of MetS in PCOS (OR: 2.133; 95% CI 1.020–4.464, p = 0.042), and was associated with higher systolic blood pressure (p = 0.009), total cholesterol (p = 0.040), and LDL-cholesterol (p = 0.038) in both PCOS and control groups (two-way ANOVA). The frequencies of VDR haplotypes were similar in PCOS and control women.ConclusionsThe present results suggest that the Apa-I variant in VDR gene may be associated with MetS in southern Brazilian women with PCOS, and with blood pressure, total cholesterol, and LDL-c in women with and without PCOS.

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Immunohistochemical evaluation of vitamin D receptor (VDR) expression in cutaneous melanoma tissues and four VDR gene polymorphisms

Cited by 16 publications

References 57 publications

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

Antiproliferative Activity of Non-Calcemic Vitamin D Analogs on Human Melanoma Lines in Relation to VDR and PDIA3 Receptors

BsmI (rs1544410) and FokI (rs2228570) vitamin D receptor polymorphisms, smoking, and body mass index as risk factors of cutaneous malignant melanoma in northeast Italy

Apa-I polymorphism in VDR gene is related to metabolic syndrome in polycystic ovary syndrome: a cross-sectional study

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