Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors

We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from ep...

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Main Authors: Catia Pilon, Andrea Rebellato, Riccardo Urbanet, Vincenza Guzzardo, Rocco Cappellesso, Hironobu Sasano, Ambrogio Fassina, Francesco Fallo
Format: Article
Language:English
Published: Wiley 2015-01-01
Series:International Journal of Endocrinology
Online Access:http://dx.doi.org/10.1155/2015/375349
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author Catia Pilon
Andrea Rebellato
Riccardo Urbanet
Vincenza Guzzardo
Rocco Cappellesso
Hironobu Sasano
Ambrogio Fassina
Francesco Fallo
author_facet Catia Pilon
Andrea Rebellato
Riccardo Urbanet
Vincenza Guzzardo
Rocco Cappellesso
Hironobu Sasano
Ambrogio Fassina
Francesco Fallo
author_sort Catia Pilon
collection DOAJ
description We previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis.
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spelling doaj-art-9a33cb739b974a2090f96d29d1bc8afe2025-02-03T00:59:58ZengWileyInternational Journal of Endocrinology1687-83371687-83452015-01-01201510.1155/2015/375349375349Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal TumorsCatia Pilon0Andrea Rebellato1Riccardo Urbanet2Vincenza Guzzardo3Rocco Cappellesso4Hironobu Sasano5Ambrogio Fassina6Francesco Fallo7Clinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, ItalyClinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, ItalyClinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, ItalyCytopathology Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, ItalyCytopathology Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, ItalyDepartment of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, JapanCytopathology Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, ItalyClinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, ItalyWe previously showed a decreased expression of vitamin D receptor (VDR) mRNA/protein in a small group of adrenocortical carcinoma (ACC) tissues, suggesting the loss of a protective role of VDR against malignant cell growth in this cancer type. Downregulation of VDR gene expression may result from epigenetics events, that is, methylation of cytosine nucleotide of CpG islands in VDR gene promoter. We analyzed methylation of CpG sites in the VDR gene promoter in normal adrenals and adrenocortical tumor samples. Methylation of CpG-rich 5′ regions was assessed by bisulfite sequencing PCR using bisulfite-treated DNA from archival microdissected paraffin-embedded adrenocortical tissues. Three normal adrenals and 23 various adrenocortical tumor samples (15 adenomas and 8 carcinomas) were studied. Methylation in the promoter region of VDR gene was found in 3/8 ACCs, while no VDR gene methylation was observed in normal adrenals and adrenocortical adenomas. VDR mRNA and protein levels were lower in ACCs than in benign tumors, and VDR immunostaining was weak or negative in ACCs, including all 3 methylated tissue samples. The association between VDR gene promoter methylation and reduced VDR gene expression is not a rare event in ACC, suggesting that VDR epigenetic inactivation may have a role in adrenocortical carcinogenesis.http://dx.doi.org/10.1155/2015/375349
spellingShingle Catia Pilon
Andrea Rebellato
Riccardo Urbanet
Vincenza Guzzardo
Rocco Cappellesso
Hironobu Sasano
Ambrogio Fassina
Francesco Fallo
Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors
International Journal of Endocrinology
title Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors
title_full Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors
title_fullStr Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors
title_full_unstemmed Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors
title_short Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors
title_sort methylation status of vitamin d receptor gene promoter in benign and malignant adrenal tumors
url http://dx.doi.org/10.1155/2015/375349
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