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Efficient growth inhibition of HPV 16 E6-expressing cells by an adenovirus-expressing p53 homologue p73bold italic \beta

Das, Sanjeev and El-Deiry, Wafik S and Somasundaram, Kumaravel (2003) Efficient growth inhibition of HPV 16 E6-expressing cells by an adenovirus-expressing p53 homologue p73bold italic \beta. In: Oncogene, 22 (52). pp. 8394-8402.

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Abstract

Tumor suppressor p53 functions are downregulated in most cervical cancers, because the product of human papilloma virus (HPV) oncogene E6 binds to and inactivates p53 by promoting its degradation. p73, a p53 homologue, is similar to p53 in structure and function but yet not degraded by HPV E6 gene product. In this study, we have developed a replication-deficient recombinant adenovirus, which expresses p73 \beta (Ad-p73). Infection of human cancer cells with Ad-p73 results in several fold increase of p73 \beta levels as well as its known target genes like $p21^{WAF1/CIP1}$. Ad-p73-infected cells showed reduced cellular DNA synthesis, arrest in G1 phase of cell cycle and induction of apoptosis. Ad-p73 inhibited the growth of cancer cells of different types. More importantly, Ad-p73 inhibited the growth of cell lines carrying HPV E6 gene, which was introduced by stable integration, more efficiently in comparison to an Ad-p53. Furthermore, Ad-p73 also inhibited the growth of HeLa cells, a cell line derived from cervical cancer, very efficiently. The ability of Ad-p73 to inhibit the growth of HPV E6-expressing cells and HeLa cells correlated with the stable expression of functional p73 in the presence of E6. These results suggest that Ad-p73 could be used as a potential gene therapy agent against cervical cancer.

Item Type: Journal Article
Additional Information: The Copyright belongs to Nature Publishing Group.
Keywords: p53;p73;human papilloma virus;cervical cancer;E6;gene therapy
Department/Centre: Division of Biological Sciences > Microbiology & Cell Biology
Date Deposited: 26 Apr 2006
Last Modified: 27 Aug 2008 11:55
URI: http://eprints.iisc.ernet.in/id/eprint/6484

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