Efficient growth inhibition of HPV 16 E6-expressing cells by an adenovirus-expressing p53 homologue p73beta |
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Authors: | Das Sanjeev El-Deiry Wafik S Somasundaram Kumaravel |
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Institution: | Department of Microbiology and Cell Biology, Indian Institute of Science, Bangalore 560 012, India. |
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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 p73beta (Ad-p73). Infection of human cancer cells with Ad-p73 results in several fold increase of p73beta 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. |
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