An intact retinoblastoma protein-binding site in Merkel cell polyomavirus large T antigen is required for promoting growth of Merkel cell carcinoma cells

Int J Cancer. 2012 Feb 15;130(4):847-56. doi: 10.1002/ijc.26076. Epub 2011 Apr 27.


Merkel cell carcinoma (MCC) is a highly aggressive skin cancer that frequently harbours Merkel cell polyomavirus (MCV) DNA integrated in the genome of the tumor cells. In our study, we elaborate our recent finding that MCV-positive MCC cell lines require the expression of the viral T antigens (TA). Indeed, in a xeno-transplantation model, we prove that TA expression is essential also in an in vivo situation, as knock down of TA leads to tumor regression. Moreover, rescuing TA short hairpin RNA (shRNA)-treated MCV-positive MCC cells by ectopic expression of shRNA-insensitive TAs clearly demonstrates that the observed effect is caused by TA knockdown. Notably, introduction of a mutation in the LTA protein interfering with LTA binding to the retinoblastoma protein (RB) ablated this rescue. The importance of this interaction was further confirmed as LTA-specific knockdown leads to explicit cell growth inhibition. In summary, the presented data demonstrate that established MCV-positive MCC tumors critically depend on TA expression, in particular the LTA and RB interaction, for sustained tumor growth. Consequently, interference with LTA/RB interaction appears as promising strategy to treat MCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / physiology*
  • Binding Sites
  • Carcinoma, Merkel Cell / pathology*
  • Cell Line, Tumor
  • Cell Proliferation
  • Doxycycline / pharmacology
  • Humans
  • Merkel cell polyomavirus / immunology*
  • Mice
  • Mice, SCID
  • Phenotype
  • Retinoblastoma Protein / metabolism*
  • Skin Neoplasms / pathology*


  • Antigens, Polyomavirus Transforming
  • Retinoblastoma Protein
  • Doxycycline