Neuroendocrine Key Regulator Gene Expression in Merkel Cell Carcinoma.

Neuroendocrine Key Regulator Gene Expression in Merkel Cell Carcinoma. Neoplasia. 2018 Nov 07;20(12):1227-1235 Authors: Chteinberg E, Sauer CM, Rennspiess D, Beumers L, Schiffelers L, Eben J, Haugg A, Winnepenninckx V, Kurz AK, Speel EJ, Zenke M, Zur Hausen A 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 RE1 silencing transcription factor (REST), neurogenic differentiation 1 (NeuroD1) 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 cel...
Source: Neoplasia - Category: Cancer & Oncology Authors: Tags: Neoplasia Source Type: research