title: Methylation Status of Vitamin D Receptor Gene Promoter in Benign and Malignant Adrenal Tumors.
abstract: 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.
authors: Clinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Catia
authors: C
authors: Pilon
authors: Clinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Andrea
authors: A
authors: Rebellato
authors: Clinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Riccardo
authors: R
authors: Urbanet
authors: Cytopathology Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Vincenza
authors: V
authors: Guzzardo
authors: Cytopathology Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Rocco
authors: R
authors: Cappellesso
authors: Department of Pathology, Tohoku University Graduate School of Medicine, Sendai 980-8575, Japan.
authors: Hironobu
authors: H
authors: Sasano
authors: Cytopathology Unit, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Ambrogio
authors: A
authors: Fassina
authors: Clinica Medica 3, Department of Medicine-DIMED, University of Padova, 35128 Padova, Italy.
authors: Francesco
authors: 0000-0002-7511-0226
authors: F
authors: Fallo