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Histone Deacetylase Inhibitors Restore Cell Surface Expression of the Coxsackie Adenovirus Receptor and Enhance CMV Promoter Activity in Castration-Resistant Prostate Cancer Cells
Joint Authors
Onicescu, Georgiana
Kasman, Laura
Voelkel-Johnson, Christina
Source
Issue
Vol. 2012, Issue 2012 (31 Dec. 2012), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2012-01-12
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
Adenoviral gene therapy using the death receptor ligand TRAIL as the therapeutic transgene can be safely administered via intraprostatic injection but has not been evaluated for efficacy in patients.
Here we investigated the efficacy of adenoviral TRAIL gene therapy in a model of castration resistant prostate cancer and found that intratumoral injections can significantly delay tumor growth but cannot eliminate established lesions.
We hypothesized that an underlying cause is inefficient adenoviral delivery.
Using the LNCaP progression model of prostate cancer we show that surface CAR expression decreases with increasing tumorigenicity and that castration resistant C4-2b cells were more difficult to transduce with adenovirus than castration sensitive LNCaP cells.
Many genes, including CAR, are epigenetically silenced during transformation but a new class of chemotherapeutic agents, known as histone deacetylase inhibitors (HDACi), can reverse this process.
We demonstrate that HDACi restore CAR expression and infectivity in C4-2b cells and enhance caspase activation in response to infection with a TRAIL adenovirus.
We also show that in cells with high surface CAR expression, HDACi further enhance transgene expression from the CMV promoter.
Thus HDACi have multiple beneficial effects, which may enhance not only viral but also non-viral gene therapy of castration resistant prostate cancer.
American Psychological Association (APA)
Kasman, Laura& Onicescu, Georgiana& Voelkel-Johnson, Christina. 2012. Histone Deacetylase Inhibitors Restore Cell Surface Expression of the Coxsackie Adenovirus Receptor and Enhance CMV Promoter Activity in Castration-Resistant Prostate Cancer Cells. Prostate Cancer،Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-448633
Modern Language Association (MLA)
Kasman, Laura…[et al.]. Histone Deacetylase Inhibitors Restore Cell Surface Expression of the Coxsackie Adenovirus Receptor and Enhance CMV Promoter Activity in Castration-Resistant Prostate Cancer Cells. Prostate Cancer No. 2012 (2012), pp.1-8.
https://search.emarefa.net/detail/BIM-448633
American Medical Association (AMA)
Kasman, Laura& Onicescu, Georgiana& Voelkel-Johnson, Christina. Histone Deacetylase Inhibitors Restore Cell Surface Expression of the Coxsackie Adenovirus Receptor and Enhance CMV Promoter Activity in Castration-Resistant Prostate Cancer Cells. Prostate Cancer. 2012. Vol. 2012, no. 2012, pp.1-8.
https://search.emarefa.net/detail/BIM-448633
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-448633