Biomaterial Database

Merkel Cell Polyomavirus Small T Antigen Initiates Merkel Cell Carcinoma-like Tumor Development in Mice. 2017

Monique E Verhaegen, and Doris Mangelberger, and Paul W Harms, and Markus Eberl, and Dawn M Wilbert, and Julia Meireles, and Christopher K Bichakjian, and Thomas L Saunders, and Sunny Y Wong, and Andrzej A Dlugosz

Department of Dermatology, University of Michigan, Ann Arbor, Michigan.

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.

UI	MeSH Term	Description	Entries
D007150	Immunohistochemistry	Histochemical localization of immunoreactive substances using labeled antibodies as reagents.	Immunocytochemistry,Immunogold Techniques,Immunogold-Silver Techniques,Immunohistocytochemistry,Immunolabeling Techniques,Immunogold Technics,Immunogold-Silver Technics,Immunolabeling Technics,Immunogold Silver Technics,Immunogold Silver Techniques,Immunogold Technic,Immunogold Technique,Immunogold-Silver Technic,Immunogold-Silver Technique,Immunolabeling Technic,Immunolabeling Technique,Technic, Immunogold,Technic, Immunogold-Silver,Technic, Immunolabeling,Technics, Immunogold,Technics, Immunogold-Silver,Technics, Immunolabeling,Technique, Immunogold,Technique, Immunogold-Silver,Technique, Immunolabeling,Techniques, Immunogold,Techniques, Immunogold-Silver,Techniques, Immunolabeling
D008822	Mice, Transgenic	Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.	Transgenic Mice,Founder Mice, Transgenic,Mouse, Founder, Transgenic,Mouse, Transgenic,Mice, Transgenic Founder,Transgenic Founder Mice,Transgenic Mouse
D004195	Disease Models, Animal	Naturally-occurring or experimentally-induced animal diseases with pathological processes analogous to human diseases.	Animal Disease Model,Animal Disease Models,Disease Model, Animal
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D000957	Antigens, Viral, Tumor	Those proteins recognized by antibodies from serum of animals bearing tumors induced by viruses; these proteins are presumably coded for by the nucleic acids of the same viruses that caused the neoplastic transformation.	Antigens, Neoplasm, Viral,Neoplasm Antigens, Viral,T Antigens,Tumor Antigens, Viral,Viral Tumor Antigens,Virus Transforming Antigens,Large T Antigen,Large T-Antigen,Small T Antigen,Small T-Antigen,T Antigen,T-Antigen,Viral T Antigens,Antigen, Large T,Antigen, Small T,Antigen, T,Antigens, T,Antigens, Viral Neoplasm,Antigens, Viral T,Antigens, Viral Tumor,Antigens, Virus Transforming,T Antigen, Large,T Antigen, Small,T Antigens, Viral,T-Antigen, Large,T-Antigen, Small,Transforming Antigens, Virus,Viral Neoplasm Antigens
D012878	Skin Neoplasms	Tumors or cancer of the SKIN.	Cancer of Skin,Skin Cancer,Cancer of the Skin,Neoplasms, Skin,Cancer, Skin,Cancers, Skin,Neoplasm, Skin,Skin Cancers,Skin Neoplasm
D014412	Tumor Virus Infections	Infections produced by oncogenic viruses. The infections caused by DNA viruses are less numerous but more diverse than those caused by the RNA oncogenic viruses.	Fibroma, Shope,Papilloma, Shope,Infections, Tumor Virus,Infection, Tumor Virus,Shope Fibroma,Shope Papilloma,Tumor Virus Infection
D015266	Carcinoma, Merkel Cell	A carcinoma arising from MERKEL CELLS located in the basal layer of the epidermis and occurring most commonly as a primary neuroendocrine carcinoma of the skin. Merkel cells are tactile cells of neuroectodermal origin and histologically show neurosecretory granules. The skin of the head and neck are a common site of Merkel cell carcinoma, occurring generally in elderly patients. (Holland et al., Cancer Medicine, 3d ed, p1245)	Merkel Cell Tumor,Merkel Cell Cancer,Merkel Cell Carcinoma,Merkle Tumors,Cancer, Merkel Cell,Cell Cancer, Merkel,Tumor, Merkel Cell,Tumors, Merkle
D016133	Polymerase Chain Reaction	In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.	Anchored PCR,Inverse PCR,Nested PCR,PCR,Anchored Polymerase Chain Reaction,Inverse Polymerase Chain Reaction,Nested Polymerase Chain Reaction,PCR, Anchored,PCR, Inverse,PCR, Nested,Polymerase Chain Reactions,Reaction, Polymerase Chain,Reactions, Polymerase Chain