Houben et al.: Merkel cell polyomavirus-infected Merkel cell carcinoma cells require expression of viral T antigens

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. [OPEN ACCESS] PubMed PUBMED Central FullText FullText_MUG

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.


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