Article Text

other Versions

PDF
Methylation of Socs-3 and Socs-1 in the carcinogenesis of Barrett's adenocarcinoma
  1. Iris Tischoff
  1. University of Bochum, Institute of Pathology, Germany
    1. Ulrich R Hengge (ulrich.hengge{at}uni-duesseldorf.de)
    1. Dept. of Dermatology, Heinrich-Heine-University, Düsseldorf, Germany
      1. Michael Vieth
      1. Clinic of Bayreuth, Institute of Pathology, Germany
        1. Christian Ell
        1. HSK-Clinics Wiesbaden, Clinic of Internal Medicine II, Germany
          1. Manfred Stolte
          1. Clinic of Bayreuth, Institute of Pathology, Germany
            1. Anette Weber
            1. University of Leipzig, Clinic of ENT Surgery, Germany
              1. Wolfgang E. Schmidt
              1. University of Bochum, St. Josef Hospital, Department of Internal Medicine I, Germany
                1. Andrea Tannapfel (andrea.tannapfel{at}rub.de)
                1. University of Bochum, Institute of Pathology, Germany

                  Abstract

                  Background: The suppressors of cytokine signaling (SOCS) are inhibitors of cytokine signaling; methylation of SOCS-3 has been implicated in the tumorigenesis of liver and head and neck cancer.

                  Aims: This study was performed to elucidate the role of SOCS-1 and SOCS-3 in Barrett adenocarcinoma and its precursor lesions.

                  Methods: After microdissection, DNA of 19 Barrett's adenocarcinomas, 56 Barrett's intraepithelial neoplasias (n = 29 low grade [LGIN] and n = 27 high grade [HGIN]), 30 Barrett's mucosa without neoplasia, 20 samples of normal squamous, gastric epithelium as well as four cell lines were studied by using methylation- specific PCR (MSP) for the SOCS-1 and SOCS-3 promoter. The presence of SOCS-3 mRNA transcripts was confirmed by semiquantitative real-time PCR, and the SOCS-3 protein was analyzed immunohistochemically.

                  Results: In normal squamous epithelium and normal gastric mucosa, neither SOCS-3 nor SOCS-1 methylation was observed. In Barrett's mucosa without intraepithelial neoplasia, SOCS-3 methylation occurred in 4/30 cases (13%) whereas SOCS-1 was unmethylated. A hypermethylated SOCS-3 promotor was found in 14/19 Barrett's adenocarcinoma (74%) and in 20/29 high and 6/27 low grade intraepithelial neoplasias (69% and 22%, respectively). SOCS-1 promoter hypermethylation occurred in 8/19 adenocarcinoma (42%) and in 6/29 high grade and 1/27 low grade intraepithelial neoplasias (21% and 4%, respectively). Methylation of the SOCS-3 promoter correlated with downregulation of SOCS-3 transcripts and protein expression in these tumors and various cell lines. In the cell lines tested, SOCS-3 and SOCS-1 transcripts increased upon treatment with the demethylation compound 5-aza-2-deoxycytidine (5-AZA- DC).

                  Conclusions: These data indicate, that promoter methylation and subsequent transcript downregulation of SOCS-3 transcripts and, to a much lesser extent, SOCS-1 are involved in the multistep carcinogenesis of Barrett's adenocarcinoma.

                  • Barrett
                  • SOCS-1
                  • SOCS-3
                  • methylation
                  • neoplasia

                  Statistics from Altmetric.com

                  Request permissions

                  If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

                  Linked Articles

                  • Digest
                    Robin Spiller Emad El-Omar