Merkel cell polyomavirus (MCPyV) causes the majority of human Merkel cell
carcinomas (MCC), a rare but highly aggressive form of
skin cancer. We recently reported that constitutive expression of MCC
tumor-derived MCPyV
tumor (
T) antigens in the skin of transgenic mice leads to
hyperplasia, increased proliferation, and spontaneous epithelial
tumor development. We sought to evaluate how the MCPyV
T antigens contribute to
tumor formation in vivo using a classical, multi-stage model for
squamous cell carcinoma development. In this model, two chemical
carcinogens, DMBA and TPA, contribute to two distinct phases of
carcinogenesis-initiation and promotion, respectively-that are required for
tumors to develop. By treating the MCPyV transgenic mice with each chemical
carcinogen, we determined how the viral oncogenes contributed to
carcinogenesis. We observed that the MCPyV
T antigens synergized with the
tumor initiator DMBA, but not with the
tumor promoter TPA, cause
tumors. Therefore, the MCPyV
tumor antigens function primarily as
tumor promoters, similar to that seen with human papillomavirus (HPV)
oncoproteins. These studies provide insight into the role of MCPyV
T antigen expression in
tumor formation in vivo and contribute to our understanding of how MCPyV may function as a human DNA tumor virus.