TY  - JOUR
A1  - Houben, Roland
A1  - Ebert, Marlies
A1  - Hesbacher, Sonja
A1  - Kervarrec, Thibault
A1  - Schrama, David
T1  - Merkel Cell Polyomavirus Large T Antigen is Dispensable in G2 and M-Phase to Promote Proliferation of Merkel Cell Carcinoma Cells
JF  - Viruses
N2  - Merkel cell carcinoma (MCC) is an aggressive skin cancer frequently caused by the Merkel cell polyomavirus (MCPyV), and proliferation of MCPyV-positive MCC tumor cells depends on the expression of a virus-encoded truncated Large T antigen (LT) oncoprotein. Here, we asked in which phases of the cell cycle LT activity is required for MCC cell proliferation. Hence, we generated fusion-proteins of MCPyV-LT and parts of geminin (GMMN) or chromatin licensing and DNA replication factor1 (CDT1). This allowed us to ectopically express an LT, which is degraded either in the G1 or G2 phase of the cell cycle, respectively, in MCC cells with inducible T antigen knockdown. We demonstrate that LT expressed only in G1 is capable of rescuing LT knockdown-induced growth suppression while LT expressed in S and G2/M phases fails to support proliferation of MCC cells. These results suggest that the crucial function of LT, which has been demonstrated to be inactivation of the cellular Retinoblastoma protein 1 (RB1) is only required to initiate S phase entry.
KW  - Merkel cell polyomavirus
KW  - large T antigen
KW  - cell cycle
KW  - Merkel cell carcinoma
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-218171
SN  - 1999-4915
VL  - 12
IS  - 10
ER  - 
TY  - JOUR
A1  - Kervarrec, Thibault
A1  - Samimi, Mahtab
A1  - Guyétant, Serge
A1  - Sarma, Bhavishya
A1  - Chéret, Jérémy
A1  - Blanchard, Emmanuelle
A1  - Berthon, Patricia
A1  - Schrama, David
A1  - Houben, Roland
A1  - Touzé, Antoine
T1  - Histogenesis of Merkel Cell Carcinoma: A Comprehensive Review
JF  - Frontiers in Oncology
N2  - Merkel cell carcinoma (MCC) is a primary neuroendocrine carcinoma of the skin. This neoplasia features aggressive behavior, resulting in a 5-year overall survival rate of 40%. In 2008, Feng et al. identified Merkel cell polyomavirus (MCPyV) integration into the host genome as the main event leading to MCC oncogenesis. However, despite identification of this crucial viral oncogenic trigger, the nature of the cell in which MCC oncogenesis occurs is actually unknown. In fact, several hypotheses have been proposed. Despite the large similarity in phenotype features between MCC tumor cells and physiological Merkel cells (MCs), a specialized subpopulation of the epidermis acting as mechanoreceptor of the skin, several points argue against the hypothesis that MCC derives directly from MCs. Alternatively, MCPyV integration could occur in another cell type and induce acquisition of an MC-like phenotype. Accordingly, an epithelial as well as a fibroblastic or B-cell origin of MCC has been proposed mainly based on phenotype similarities shared by MCC and these potential ancestries. The aim of this present review is to provide a comprehensive review of the current knowledge of the histogenesis of MCC.
KW  - merkel cell polyomavirus (MCPyV)
KW  - epithelial
KW  - fibroblast
KW  - B cell
KW  - Merkel cell carcinoma (MCC)
KW  - histogenesis
KW  - origin
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-325733
VL  - 9
ER  -