Advance Access publication February 1, 2010 Epigenetic repression of E-cadherin by human papillomavirus 16 E7 protein

A common feature shared between several human cancer-associated viruses, such as Epstein-Barr virus, Hepatitis B virus and Hepatitis C virus, and Human papillomavirus (HPV) is the ability to reduce the expression of cellular E-cadherin. Since E-cadherin is used by Langerhans cells to move through the stratified epithelium, its re-duction may affect the efficiency by which the immune system re-sponds to HPV infection and the length of persistent HPV infections. We observed that the E7 protein of this virus (HPV16) is most efficient at reducing E-cadherin levels. This E7 activity is indepen-dent of retinoblastoma protein or AP-2a degradation. Instead it is associated with augmentation of cellular DNA methyltransferase I (Dnmt1) activity. Significantly, inhibition of Dnmt activity re-estab-lished E-cadherin levels of the cells, presenting the possibility that similar epigenetic intervention clinically may be a way to re-estab-lish the influx of Langerhans cells into infected epithelium to coun-teract HPV persistence