Marked Increase in <i>CYP24A1</i> Gene Expression in Human Papillary Thyroid Cancer

Balla, Bernadett; Kósa, János P.; Tobiás, Bálint; Halászlaki, Csaba; Takács, István; Horváth, Hajnalka; Szabó, Gábor; Nagy, Zsolt; Horanyi, J; Járay, Balázs; Székely, Eszter; Lakatos, Péter

doi:10.1089/thy.2010.0420

Cited by 20 publications

(19 citation statements)

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“…Recently, fibroblast growth factor 23 (FGF23) was identified as a novel antagonist of PTH and is thought to play an important role in vitamin D regulation pathway (84). Although CYP27B1 and CYP24A1 are primarily expressed in the kidney, recent studies showed that they are expressed in many other tissues, including the thyroid (61, 62). In TC, there is evidence that polymorphisms leading to impaired CYP27B1 function and/or increased CYP24A1 activity are associated with increased TC risk (49).…”

Section: Resultsmentioning

confidence: 99%

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Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: the case of thyroid cancer

et al. 2014

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Vitamin D is a key regulator of calcium metabolism and has been implicated as a cancer preventive agent. However, clinical studies have revealed conflicting results on its cancer preventive properties, attributed in part to multiple metabolic and regulatory factors susceptible to affect individual responses to exogenous vitamin D. Vitamin D is obtained from dietary sources and sun exposure, which depends on numerous parameters such as skin type, latitude, and lifestyle factors. Focusing on thyroid cancer (TC), we document that genetic and epigenetic determinants can greatly impact individual response to vitamin D and may outweigh the classical clinical correlative studies that focus on sun exposure/dietary intake factors. In particular, genetic determinants innate to host intrinsic metabolic pathways such as highly polymorphic cytochromes P450s responsible for the metabolic activation of vitamin D are expressed in many organs, including the thyroid gland and can impact vitamin D interaction with its nuclear receptor (VDR) in thyroid tissue. Moreover, downstream regulatory pathways in vitamin D signaling as well as VDR are also subject to wide genetic variability among human populations as shown by genome-wide studies. These genetic variations in multiple components of vitamin D pathways are critical determinants for the revaluation of the potential preventive and anticancer properties of vitamin D in TC.

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Section: Resultsmentioning

confidence: 99%

“…In TC, there is evidence that polymorphisms leading to impaired CYP27B1 function and/or increased CYP24A1 activity are associated with increased TC risk (49). Transcriptional profiling studies show that both enzymes are overexpressed in early TC (61), but their expression tends to decrease along with tumor progression (64, 66). …”

Section: Resultsmentioning

confidence: 99%

Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: the case of thyroid cancer

et al. 2014

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“…Ezzel ellentétben a hormont inaktiváló CYP24A1 enzim mRNS-e nem expresszálódott a nem tumoros májszövetben, ugyanakkor a hepatocellularis carcinomaszövetek nagy részében kimutatható volt. A hepatocellularis carcinomában talált eredményeink megegyeznek az irodalomban ismert emberi malignus vastagbél-, prosztata-, pajzsmirigy-és nyelőcsőda-ganatokban leírt eredményekkel [32,42,43,52,53]. A CYP24A1-expresszió mértéke negatív összefüggést mutatott a prognózissal tüdő-adenocarcinomában [54].…”

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A D-vitamin metabolizmusa humán hepatocellularis carcinomában és az azt körülvevő tumormentes májszövetben

et al. 2016

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Bevezetés: Az 1,25-dihidroxi-D 3 -vitamin tumorellenes hatása hepatocellularis carcinomában már részben ismert. Cél-kitűzés: Az 1,25-dihidroxi-D 3 -vitamint inaktiváló CYP24A1-mRNS-és fehérjeexpresszió, az aktiváló CYP27B1-és a VDR-mRNS-expresszió mértékének összehasonlítása humán hepatocellularis carcinomában és az azt körülvevő tumormentes májszövetben. Módszer: 13 beteg friss fagyasztott májszövetmintáját a CYP24A1-mRNS-és fehérje-, 36 beteg paraffinba ágyazott májszövetmintáját használtuk a VDR-és a CYP27B1-mRNS-expresszió kimutatására. Az mRNS-expressziót RT-PCR-rel, a fehérjét immunhisztokémiai vizsgálatokkal mértük. Eredmények: A hepatocellularis carcinomaminták többségében kimutatható volt a CYP24A1-mRNS-expresszió, míg a nem tumoros májszö-vetminták egyikében sem. A CYP27B1-és VDR-expresszió szignifikánsan alacsonyabb hepatocellularis carcinomában a tumormentes májszövethez képest (p<0,05). A CYP24A1-mRNS-expressziót fehérjeszintézis követi. Következteté-sek: A CYP24A1 inaktiváló enzim jelenléte, az aktiváló CYP27B1 és a VDR csökkent expressziója humán hepatocellularis carcinomában a D-vitamin csökkent helyi aktivitására enged következtetni, mint egy menekülő mechanizmus a tumor részéről a D-vitamin antitumorhatása ellen. Orv. Hetil., 2016, 157(48), 1910-1918. Kulcsszavak: hepatocellularis carcinoma, CYP24A1, CYP27B1, D-vitamin Vitamin D metabolism and signaling in human hepatocellular carcinoma and surrounding non-tumorous liverIntroduction: 1,25-Dihydroxy vitamin D 3 mediates antitumor effects in hepatocellular carcinoma. Aim: We examined mRNA and protein expression differences in 1,25-Dihydroxy vitamin D 3 -inactivating CYP24A1, mRNA of activating CYP27B1 enzymes, and that of VDR between human hepatocellular carcinoma and surrounding non-tumorous liver. Methods: Snap-frozen tissues from 13 patients were studied for mRNA and protein expression of CYP24A1. Paraffin-embedded tissues from 36 patients were used to study mRNA of VDR and CYP27B1. mRNA expression was measured by RT-PCR, CYP24A1 protein was detected by immunohistochemistry. Results: Expression of VDR and CYP27B1 was significantly lower in hepatocellular carcinoma compared with non-tumorous liver (p<0.05). The majority of the HCC samples expressed CYP24A1 mRNA, but neither of the non-tumorous liver. The gene activation was followed by CYP24A1 protein synthesis. Conclusions: The presence of CYP24A1 mRNA and the reduced expression of VDR and CYP27B1 mRNA in human hepatocellular carcinoma samples indicate decreased bioavailability of 1,25-Dihydroxy vitamin D 3 , providing an escape mechanism from the anti-tumor effect.

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“…It has received considerable recent attention as it exerts effects on cell proliferation, differentiation, apoptosis, and anti-angiogenesis [3-7]. Some experimental studies have suggested that vitamin D can protect against thyroid cancer [8-11]. However, clinical evidence for an association between lower serum vitamin D levels and an increased prevalence of thyroid cancer has been inconsistent [12-18].…”

Section: Introductionmentioning

confidence: 99%

Serum vitamin D3 levels are not associated with thyroid cancer prevalence in euthyroid subjects without autoimmune thyroid disease

Choi

Kim

et al. 2017

Korean J Intern Med

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Background/AimsPrevious studies have suggested that elevated serum vitamin D levels might protect against thyroid cancer. Elevated serum thyroid stimulating hormone levels and autoimmune thyroid disease (AITD) are suggested to be thyroid cancer promoting factors but have not been well controlled in previous studies. We designed the present study to evaluate whether serum vitamin D levels are associated with thyroid cancer in euthyroid patients with no clinical evidence of AITD.MethodsThis cross-sectional study included subjects who underwent routine health check-ups, including serum 25-hydroxy vitamin D3 (25(OH)D3) levels, anti-thyroid peroxidase antibody (TPO-Ab), and thyroid ultrasonography (US). Inclusion criteria were euthyroid, negative TPO-Ab, and no evidence of AITD by US findings. Thyroid cancer diagnoses were based on fine needle aspiration cytology and/or postsurgical histopathological findings.ResultsWe enrolled 5,186 subjects (64% male, 37% female) in this study, including 53 patients (1%) with a diagnosis of thyroid cancer (33 males, 20 females). Mean 25(OH)D3 levels were similar between the thyroid cancer and control groups (p = 0.20). Subgroup analysis according to sex or seasonal variation also revealed no differences in 25(OH)D3 levels between the two groups. Based on the levels of 25(OH)D3, there was no significant difference in the prevalence of thyroid cancer; the prevalence was 0.71%, 0.94%, 1.40%, and 0.82% in the deficient, insufficient, sufficient, and excess groups, respectively (p = 0.64).ConclusionsThe levels of serum 25(OH)D3 are not associated with thyroid cancer prevalence in euthyroid subjects with no clinical evidence of AITD.

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Marked Increase in CYP24A1 Gene Expression in Human Papillary Thyroid Cancer

Cited by 20 publications

References 9 publications

Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: the case of thyroid cancer

Insights into genetic and epigenetic determinants with impact on vitamin D signaling and cancer association studies: the case of thyroid cancer

A D-vitamin metabolizmusa humán hepatocellularis carcinomában és az azt körülvevő tumormentes májszövetben

Serum vitamin D3 levels are not associated with thyroid cancer prevalence in euthyroid subjects without autoimmune thyroid disease

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