Diffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy.
Green, Katie L Southgate, Thomas D Mulryan, Kate Fairbairn, Leslie J Stern, Peter L Gaston, Kevin
Green, Katie L
Southgate, Thomas D
Mulryan, Kate
Fairbairn, Leslie J
Stern, Peter L
Gaston, Kevin
Citations
Altmetric:
Abstract
Human papillomaviruses (HPVs) are a causative agent of cervical cancer and are implicated in several other types of malignant disease including cancer of the vulva, oral cancer, and skin cancer. In HPV-transformed cells, expression of the viral E6 and E7 oncogenes increases cell proliferation and inhibits apoptosis. Expression of the viral E2 protein in HPV-transformed cells represses transcription of E6 and E7 and induces apoptosis and/or growth arrest. We have shown previously that herpes simplex virus type 1 (HSV-1) VP22-HPV E2 fusion proteins can traffic between cells and induce apoptosis. Here we show that replication-defective adenoviruses can be used to deliver VP22-E2 fusion proteins to target cells. We show that the use of adenoviral vectors to deliver VP22-E2 proteins leads to high levels of apoptosis. Interestingly, VP22-E2 proteins produced in adenovirus-infected cells are able to enter uninfected cells and induce apoptosis. Trafficking between cells and the induction of apoptosis in bystander cells are detectable in a three-dimensional tumor model. These results suggest that adenoviral vectors expressing VP22-E2 fusion proteins could be used to treat cervical cancer and other HPV-associated diseases.
Description
Date
2006-02
Publisher
Collections
Keywords
Uterine Cervical Cancer
Type
Article
Citation
Diffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy. 2006, 17 (2):147-57 Hum. Gene Ther.