Diffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy.

2.50
Hdl Handle:
http://hdl.handle.net/10541/72737
Title:
Diffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy.
Authors:
Green, Katie L; Southgate, Thomas D; Mulryan, Kate; Fairbairn, Leslie J; Stern, Peter L; Gaston, Kevin
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.
Affiliation:
Department of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.
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.
Journal:
Human Gene Therapy
Issue Date:
Feb-2006
URI:
http://hdl.handle.net/10541/72737
DOI:
10.1089/hum.2006.17.147
PubMed ID:
16454648
Type:
Article
Language:
en
ISSN:
1043-0342
Appears in Collections:
All Paterson Institute for Cancer Research

Full metadata record

DC FieldValue Language
dc.contributor.authorGreen, Katie L-
dc.contributor.authorSouthgate, Thomas D-
dc.contributor.authorMulryan, Kate-
dc.contributor.authorFairbairn, Leslie J-
dc.contributor.authorStern, Peter L-
dc.contributor.authorGaston, Kevin-
dc.date.accessioned2009-07-07T11:15:59Z-
dc.date.available2009-07-07T11:15:59Z-
dc.date.issued2006-02-
dc.identifier.citationDiffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy. 2006, 17 (2):147-57 Hum. Gene Ther.en
dc.identifier.issn1043-0342-
dc.identifier.pmid16454648-
dc.identifier.doi10.1089/hum.2006.17.147-
dc.identifier.urihttp://hdl.handle.net/10541/72737-
dc.description.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.en
dc.language.isoenen
dc.subjectUterine Cervical Canceren
dc.subject.meshAdenoviridae-
dc.subject.meshAnimals-
dc.subject.meshApoptosis-
dc.subject.meshBystander Effect-
dc.subject.meshCulture Media, Conditioned-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshDiffusion-
dc.subject.meshFemale-
dc.subject.meshGene Therapy-
dc.subject.meshGenetic Vectors-
dc.subject.meshHela Cells-
dc.subject.meshHuman papillomavirus 16-
dc.subject.meshHumans-
dc.subject.meshOncogene Proteins, Viral-
dc.subject.meshRecombinant Fusion Proteins-
dc.subject.meshUterine Cervical Neoplasms-
dc.subject.meshViral Structural Proteins-
dc.subject.meshVirus Replication-
dc.titleDiffusible VP22-E2 protein kills bystander cells and offers a route for cervical cancer gene therapy.en
dc.typeArticleen
dc.contributor.departmentDepartment of Biochemistry, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, UK.en
dc.identifier.journalHuman Gene Therapyen

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