Human Papillomaviruses (HPVs) are involved in the etiology of at least 10% of all human cancers and are mainly implicated in the development of pre-malignant and malignant lesions of the ano-genital tract. In particular, genital High-Risk HPVs are responsible for nearly 100% of cases of cervical cancer, which represents the second most prevalent cancer in women worldwide. The carcinogenic risk associated with HPV infection is primarily due to the activity of two viral oncoproteins, E6 and E7. Indeed, their expression is necessary for the maintenance of the malignant phenotype, and is always retained in HPV-positive cancer cells. Although malignant transformation results from the synergistic and complementary effects of E6 and E7, the latter is reported to be the main oncoprotein of HPVs. One of the major aims of this review is to update the understanding of the role of E7 in HPV-associated carcinogenesis, focusing on the binding with its cellular targets and the effects induced by these associations. The interaction of E7 with its main target, the tumor suppressor protein retinoblastoma (pRb), will be described, with emphasis on the biological consequences and the domains involved. However, as E7 oncogenic properties are not only attributable to this association, the significance of other relevant interactions will be evaluated as well. Due to the essential role of E7 in cervical carcinogenesis, the lack of homology with cellular proteins and the exclusive expression in cancer cells, this oncoprotein represents the main target for cervical cancer therapy. The therapeutic potential of strategies aimed at E7 inhibition for the treatment of HPV-associated lesions will be addressed. Among others, the use of small interfering RNA (siRNA), intracellular antibodies ("intrabodies"), ribozymes, anti-sense oligonucleotides and aptamers to knock out E7 at the gene/protein level will be covered. The results of these studies will be reviewed with the aim of highlighting E7 inhibition as a promising approach for the treatment of HPV-associated cancer.
|Title of host publication||Oncoproteins: Types and Detection|
|Publisher||Nova Science Publishers, Inc.|
|Number of pages||43|
|Publication status||Published - Jan 2011|
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