Diffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy.
AuthorsGreen, Katie L
Southgate, Thomas D
Fairbairn, Leslie J
Stern, Peter L
AffiliationDepartment of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
MetadataShow full item record
AbstractHuman 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.
CitationDiffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy. 2006, 17 (2):147-57 Hum. Gene Ther.
JournalHuman Gene Therapy
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