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Supplementary Figures S1-S2 and Supplementary Tables S1-S2 from Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice

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posted on 2023-03-31, 00:30 authored by Monique E. Verhaegen, Doris Mangelberger, Paul W. Harms, Markus Eberl, Dawn M. Wilbert, Julia Meireles, Christopher K. Bichakjian, Thomas L. Saunders, Sunny Y. Wong, Andrzej A. Dlugosz

Supplementary Figure S1. Transgenic constructs and validation of transgene expression in vivo. Supplementary Figure S2. Paranuclear dot-like expression of K8 and K5 in mouse MCC-like tumors. Supplementary Table S1. Correlation between transgene expression level, based on immunostaining, and phenotype severity. Supplementary Table S2.Primary antibodies and dilutions.

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University of Michigan

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ARTICLE ABSTRACT

Merkel cell carcinoma (MCC) tumor cells express several markers detected in normal Merkel cells, a nonproliferative population of neuroendocrine cells that arise from epidermis. MCCs frequently contain Merkel cell polyomavirus (MCPyV) DNA and express viral transforming antigens, sT and tLT, but the role of these putative oncogenes in MCC development, and this tumor's cell of origin, are unknown. Using a panel of preterm transgenic mice, we show that epidermis-targeted coexpression of sT and the cell fate-determinant atonal bHLH transcription factor 1 (ATOH1) leads to development of widespread cellular aggregates, with histology and marker expression mimicking that of human intraepidermal MCC. The MCC-like tumor phenotype was dependent on the FBXW7-binding domain of sT, but not the sT-PP2A binding domain. Coexpression of MCPyV tLT did not appreciably alter the phenotype driven by either sT or sT combined with ATOH1. MCPyV sT, when coexpressed with ATOH1, is thus sufficient to initiate development of epidermis-derived MCC-like tumors in mice. Cancer Res; 77(12); 3151–7. ©2017 AACR.

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