Neuroendocrine Key Regulator Gene Expression in Merkel Cell Carcinoma

Emil Chteinberg, Christopher Martin Sauer, Dorit Rennspiess, Lukas Beumers, Lisa Schiffelers, Jonathan Eben, Anke Haugg, Veronique Winnepenninckx, Anna Kordelia Kurz, Ernst-Jan Speel, Martin Zenke, Axel zur Hausen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

12 Citations (Web of Science)

Abstract

Merkel cell carcinoma (MCC) is a highly aggressive non-melanoma skin cancer of the elderly which is associated with the Merkel cell polyomavirus (MCPyV). MCC reveals a trilinear differentiation characterized by neuroendocrine, epithelial and pre/pro B-cell lymphocytic gene expression disguising the cellular origin of MCC. Here we investigated the expression of the neuroendocrine key regulators RE 1 silencing transcription factor (REST), neurogenic differentiation 1 (NeuroDl) and the Achaete-scute homolog 1 (ASCL1) in MCC. All MCCs were devoid of REST and were positive for NeuroD1 expression. Only one MCC tissue revealed focal ASCL1 expression. This was confirmed in MCPyV-positive MCC cell lines. Of interest, MCPyV-negative cell lines did express REST. The introduction of REST expression in REST-negative, MCPyV-positive MCC cells downregulated the neuroendocrine gene expression. The lack of the neuroendocrine master regulator ASCL1 in almost all tested MCCs points to an important role of the absence of the negative regulator REST towards the MCC neuroendocrine phenotype. This is underlined by the expression of the REST-regulated microRNAs miR-9/9* in REST-negative MCC cell lines. These data might provide the basis for the understanding of neuroendocrine gene expression profile which is expected to help to elucidate the cellular origin of MCC.

Original languageEnglish
Pages (from-to)1227-1235
Number of pages9
JournalNeoplasia (Online)
Volume20
Issue number12
DOIs
Publication statusPublished - Dec 2018

Keywords

  • RESTRICTIVE SILENCER FACTOR
  • LUNG-CANCER
  • REST
  • REPRESSOR
  • TRANSCRIPTION
  • POLYOMAVIRUS
  • DIFFERENTIATION
  • TRANSFORMATION
  • SYNAPTOPHYSIN
  • EPIDEMIOLOGY

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