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SHR Neuro Cancer Cardio Lipid Metab Microb

Houben, R; Shuda, M; Weinkam, R; Schrama, D; Feng, H; Chang, Y; Moore, PS; Becker, JC.
Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens.
J Virol. 2010; 84(14):7064-7072 Doi: 10.1128/JVI.02400-09 [OPEN ACCESS]
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Co-authors Med Uni Graz: Becker Jürgen Christian; Schrama David
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Abstract:: Merkel cell carcinoma (MCC) is the most aggressive skin cancer. Recently, it was demonstrated that human Merkel cell polyomavirus (MCV) is clonally integrated in approximately 80% of MCC tumors. However, direct evidence for whether oncogenic viral proteins are needed for the maintenance of MCC cells is still missing. To address this question, we knocked down MCV T-antigen (TA) expression in MCV-positive MCC cell lines using three different short hairpin RNA (shRNA)-expressing vectors targeting exon 1 of the TAs. The MCC cell lines used include three newly generated MCV-infected cell lines and one MCV-negative cell line from MCC tumors. Notably, all MCV-positive MCC cell lines underwent growth arrest and/or cell death upon TA knockdown, whereas the proliferation of MCV-negative cell lines remained unaffected. Despite an increase in the number of annexin V-positive, 7-amino-actinomycin D (7-AAD)-negative cells upon TA knockdown, activation of caspases or changes in the expression and phosphorylation of Bcl-2 family members were not consistently detected after TA suppression. Our study provides the first direct experimental evidence that TA expression is necessary for the maintenance of MCV-positive MCC and that MCV is the infectious cause of MCV-positive MCC.
Find related publications in this database (using NLM MeSH Indexing): Adult -; Aged -; Aged, 80 and over -; Antigens, Polyomavirus Transforming - genetics Antigens, Polyomavirus Transforming - metabolism; Carcinoma, Merkel Cell - pathology Carcinoma, Merkel Cell - virology; Cell Cycle - physiology; Cell Line, Tumor -; Cell Survival -; Female -; Gene Knockdown Techniques -; Humans -; Male -; Middle Aged -; Polyomavirus - immunology Polyomavirus - metabolism; Polyomavirus Infections - metabolism Polyomavirus Infections - pathology Polyomavirus Infections - virology; Proto-Oncogene Proteins c-bcl-2 - genetics Proto-Oncogene Proteins c-bcl-2 - metabolism; Skin Neoplasms - metabolism Skin Neoplasms - pathology Skin Neoplasms - virology