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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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 |
|---|---|
| Publication: | Oncogene |
| Publisher: | Nature Publishing Group |
| 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.ac.in/id/eprint/6484 |
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