Induction of p16 during immortalization by HPV 16 and 18 and not during malignant transformation.
Yoshifumi Nakao,Xiaolong Yang,M. Yokoyama,A. Ferenczy,Shou Ching Tang,Mary M. Pater,Alan Pater +6 more
TLDR
The results suggest that the inactivation of the p16/cdk-cyclin/Rb cascade does not occur during malignant transformation but occurs during the immortalization by HPV in HPV-harbouring premalignant lesions, the in situ equivalent of immortalized cells.Abstract:
The p16 (MTS1) tumour-suppressor gene is a cyclin-dependent kinase (cdk) inhibitor that decelerates the cell cycle by inactivating the cdks that phosphorylate the retinoblastoma tumour-suppressor gene (Rb) protein (pRb). In cervical cancers, pRb is inactivated by the HPV E7 oncoprotein or by mutations. The hypothesis of earlier reports was that the disruption of the p16/cdk-cyclin/Rb cascade is essential for malignant cervical transformation/carcinogenesis. We previously established in vitro model systems of cervical cancer representing four steps of oncogenic progression initiated by the two most common oncogenic HPVs in ectocervical and endocervical epithelial cells. This report used these systems to investigate the role of p16 in cervical cancers. A dramatic enhancement of the p16 RNA level was observed after immortalization by HPV 16 or 18. Furthermore, the p16 protein was newly observed following immortalization. However, no further changes were found for RNA or protein levels after serum selection or malignant transformation. For three cervical carcinoma cell lines, similar high levels of p16 expression were seen. Point mutations or homozygous deletions of p16 were not observed in the in vitro systems or in clinical specimens. These results suggest that the inactivation of the p16/cdk-cyclin/Rb cascade does not occur during malignant transformation but occurs during the immortalization by HPV in HPV-harbouring premalignant lesions, the in situ equivalent of immortalized cells. Also suggested is that p16 has no role in the specific malignant transformation step from immortal premalignant lesions during the carcinogenesis of HPV-initiated cervical cancers.read more
Citations
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Human Papillomavirus and Survival of Patients with Oropharyngeal Cancer
K. Kian Ang,Jonathan Harris,Richard H. Wheeler,Randal S. Weber,David I. Rosenthal,Phuc Felix Nguyen-Tân,William H. Westra,Christine H. Chung,Richard C.K. Jordan,Charles Lu,Harold Kim,Rita Axelrod,C Craig Silverman,Kevin P. Redmond,Maura L. Gillison +14 more
TL;DR: Tumor HPV status is a strong and independent prognostic factor for survival among patients with oropharyngeal cancer and the risk of death significantly increased with each additional pack-year of tobacco smoking.
Journal ArticleDOI
Forging a signature of in vivo senescence
TL;DR: It is advocated that more-specific descriptors be substituted for the now broadly applied umbrella term 'senescence' in defining the suite of diverse physiological responses to cellular stress.
Journal ArticleDOI
Expression Status of p16 Protein Is Associated with Human Papillomavirus Oncogenic Potential in Cervical and Genital Lesions
TL;DR: Marked overexpression of p16 protein was observed in all cervical cancers and preneoplastic lesions with infection by high- and intermediate-risk HPVs and thus might be attributable to differences in functional inactivation of Rb protein by different HPVs.
Journal ArticleDOI
Human papillomavirus-associated head and neck cancer is a distinct epidemiologic, clinical, and molecular entity.
TL;DR: Prophylactic and therapeutic vaccines targeted against the viral capsid components and oncoproteins will provide the ultimate evidence for a role for HPV in HNSCC, if demonstrated to be effective in the prevention or therapy of this disease.
Journal ArticleDOI
Expression of p16 protein identifies a distinct entity of tonsillar carcinomas associated with human papillomavirus.
Jens Peter Klussmann,Elif Gültekin,Soenke J. Weissenborn,Ulrike Wieland,Volker Dries,Hans Peter Dienes,Hans Edmund Eckel,Herbert Pfister,Pawel G. Fuchs +8 more
TL;DR: In this article, the p16 protein expression in 34 tonsillar carcinoma was analyzed for correlation to HPV status and load of viral DNA, and a significant correlation of p16 expression with increased disease-free survival was found.
References
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Yue Xiong,Gregory J. Hannon,Gregory J. Hannon,Hui Zhang,Hui Zhang,David J. Casso,David J. Casso,Ryuji Kobayashi,David Beach,David Beach +9 more
TL;DR: It is found that over expression of p21 inhibits the activity of each member of the cyclin/CDK family, and this results indicate that p21 may be a universal inhibitor of cyclin kinases.
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Francesc Xavier Bosch,M. M. Manos,Nubia Muñoz,Mark E. Sherman,Angela M. Jansen,Julian Peto,Mark Schiffman,Victor Moreno,Robert J. Kurman,Keerti V. Shah +9 more
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A cell cycle regulator potentially involved in genesis of many tumor types
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