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Human Papillomavirus Type 16 E7 Up-regulates AKT Activity through the Retinoblastoma Protein
Abstract
Human papillomaviruses (HPV) are small DNA tumor viruses causally associated with cervical cancer. The early gene product E7 from high-risk HPV is considered the major transforming protein expressed by the virus. Although many functions have been described for E7 in disrupting normal cellular processes, we describe in this study a new cellular target in primary human foreskin keratinocytes (HFK), the serine/threonine kinase AKT. Expression of HPV type 16 E7 in HFK caused inhibition of differentiation, hyperproliferation, and up-regulation of AKT activity in organotypic raft cultures. The ability of E7 to up-regulate AKT activity is dependent on its ability to bind to and inactivate the retinoblastoma (Rb) gene product family of proteins. Furthermore, we show that knocking down Rb alone, with short hairpin RNAs, was sufficient to up-regulate AKT activity in differentiated keratinocytes. Up-regulation of AKT activity and loss of Rb was also observed in HPV-positive cervical high-grade squamous intraepithelial lesions when compared with normal cervical tissue. Together, these data provide evidence linking inactivation of Rb by E7 in the up-regulation of AKT activity during cervical cancer progression. (Cancer Res 2006; 66(11): 5555-9)
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“the activation of AKT signalling by high-risk E7 has been linked to the downstream activation of transcription factors leading to mmp gene expression [260,265,266]”
From The Not-So-Good, the Bad and the Ugly: HPV E5, E6 and E7 Oncoproteins in the Orchestration of Carcinogenesis (2021) · cites this paper as [265]
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Research works printed but not linked: 18
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Cited by
Basukala, O., & Banks, L. (2021) · Viruses · doi:10.3390/v13101892 · Cited by 137
Genome Analysis of Latin American Cervical Cancer: Frequent Activation of the PIK3CA Pathway
Lou, H., Villagran, G., Boland, J. F., Im, K. M., Polo, S., Zhou, W., Odey, U., Juárez-Torres, E., Medina-Martínez, I., Roman-Basaure, E., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1837 · Cited by 88
Metadata
- Authors
- Menges, C. W., Baglia, L. A., Lapoint, R., & McCance, D. J.
- Affiliations
- 1Biochemistry and Biophysics, Departments of
- 2Microbiology and Immunology, and
- 3Pathology and Laboratory Medicine and
- Venue
- Cancer Research
- Published
- 2006-06-01
- Volume
- 66
- Issue
- 11
- Pages
- 5555-5559
- ISSN
- 0008-5472
- 1538-7445
- Cited by
- 145
- References
- 0
- Language
- en
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- Menges, C. W., Baglia, L. A., Lapoint, R., & McCance, D. J. (2006). Human Papillomavirus Type 16 E7 Up-regulates AKT Activity through the Retinoblastoma Protein. Cancer Research. https://doi.org/10.1158/0008-5472.can-06-0499
