Radiation-enhanced expression of E6/E7 transforming oncogenes of human papillomavirus-16 in human cervical carcinoma

Santin, Alessandro D.; Hermonat, Paul L.; Ravaggi, Antonella; Chiriva‐Internati, Maurizio; Pecorelli, Sërgio; Parham, Groesbeck P.

doi:10.1002/(sici)1097-0142(19981201)83:11<2346::aid-cncr14>3.0.co;2-g

Cited by 57 publications

(30 citation statements)

References 31 publications

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“…1). The up-regulation of MHC class I on human and mouse tumor cells in vitro has been reported in various studies following 10 -100 Gy of radiation (39,40). In addition, overexpression of ICAM-1 on tumor cells has been associated with increased sensitivity to CTL-mediated lysis (41).…”

Section: Discussionmentioning

confidence: 98%

External Beam Radiation of Tumors Alters Phenotype of Tumor Cells to Render Them Susceptible to Vaccine-Mediated T-Cell Killing

Chakraborty¹,

Abrams²,

et al. 2004

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Section: Discussionmentioning

confidence: 98%

External Beam Radiation of Tumors Alters Phenotype of Tumor Cells to Render Them Susceptible to Vaccine-Mediated T-Cell Killing

Chakraborty¹,

Abrams²,

et al. 2004

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“…Cells derived from cervical cancers with inte-grated HPV16 or HPV18 genomes, such as Ca Ski, SiHa, and HeLa cells, also demonstrate a wide range of cellular responses to TNF-, Fas-, and TRAIL-induced apoptosis, from sensitivity to resistance (7,21,22). In addition to differences in their responses to triggers of extrinsic apoptosis, Ca Ski and SiHa cells also respond differently to treatments that trigger intrinsic apoptosis in transformed cells (3,19,26,33,35). For example, Ca Ski cells were sensitive while SiHa cells were resistant to apoptosis in the absence of cell anchorage (25).…”

mentioning

confidence: 99%

Complexes of Human Papillomavirus Type 16 E6 Proteins Form Pseudo-Death-Inducing Signaling Complex Structures during Tumor Necrosis Factor-Mediated Apoptosis

Filippova

Filippov

Kagoda

et al. 2009

J Virol

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High-risk strains of human papillomavirus (HPV) such as HPV type 16 (HPV16) and HPV18 are causative agents of most human cervical carcinomas. E6, one of the oncogenes encoded by HPV16, possesses a number of biological and transforming functions. We have previously shown that the binding of E6 to host apoptotic proteins such as tumor necrosis factor (TNF) R1, the adaptor protein FADD, and procaspase 8 results in a significant modification of the normal flow of apoptotic events. For example, E6 can bind to and accelerate the degradation of FADD. In addition, full-length E6 binds to the TNF R1 death domain and can also bind to and accelerate the degradation of procaspase 8. In contrast, the binding of small splice isoforms known as E6* results in the stabilization of procaspase 8. In this report, we propose a model for the ability of HPV16 E6 to both sensitize and protect cells from TNF as well as to protect cells from Fas. We demonstrate that both the level of E6 expression and the ratio between full-length E6 and E6* are important factors in the modification of the host extrinsic apoptotic pathways and show that at high levels of E6 expression, the further sensitization of U2OS, NOK, and Ca Ski cells to TNF-mediated apoptosis is most likely due to the formation of a pseudo-death-inducing signaling complex structure that includes complexes of E6 proteins.High-risk strains of human papillomavirus (HPV) such as HPV type 16 (HPV16) and HPV18, are the causative agents of most cases of human cervical carcinomas (23). Two oncogenes encoded by these viruses, E6 and E7, are best known for their ability to inactivate the tumor suppressors p53 and Rb, respectively (34). HPV16 E6 (E6) mediates a rapid, ubiquitin-dependent degradation of the tumor suppressor p53, and the resulting loss of p53 clearly contributes to the oncogenic potential of high-risk HPVs. In addition to accelerating the degradation of p53, E6 possesses numerous other biological and transforming activities (28). These activities result from the binding of E6 to cellular proteins that are involved in a number of cellular functions such as the regulation of transcription and DNA replication, epithelial organization and differentiation, cell-cell adhesion, polarity, proliferation control, DNA repair, apoptosis, and immune evasion (36).One important host response to viral infection is the activation of one or more apoptotic pathways, a process that is often carried out through members of the tumor necrosis factor (TNF) superfamily. To overcome the elimination of infected cells through apoptosis, viruses have developed numerous ways to modify the normal course of apoptotic events (reviewed in references 12 and 14). Apoptosis mediated by members of the TNF superfamily is initiated by the binding of ligands to their corresponding receptors. This interaction leads to the recruitment of adaptor proteins and initiator caspases to the death domain (DD) of receptors, resulting in the formation of a death-inducing signaling complex (DISC). Following DISC formation, the c...

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“…[4][5][6] The two viral oncogenic proteins, E6 and E7 are commonly expressed in these carcinoma cells and are required for maintaining cancer malignancy. 7) It has been reported that, except for cervical cancers, most cancer development results from p53 gene mutation. 8) p53 mutation is detected in more than 50% of cancer cells, but rarely in cervical cancer cell types.…”

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confidence: 99%

Differential Suppression of Human Cervical Cancer Cell Growth by Adenovirus Delivery of p53 in vitro: Arrest Phase of Cell Cycle Is Dependent on Cell Line

Ahn

Han

Bae

et al. 2002

Japanese Journal of Cancer Research

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It has been reported that overexpression of wild-type p53 protein induces suppression of tumor cell growth in vivo and in vitro. In this study, we further evaluated the differential effects of p53 delivered in an adenovirus vector on the cell growth, apoptosis and cell cycle progression in cervical cancer cell lines. We constructed a recombinant adenovirus expressing p53 and then delivered this into cervical carcinoma cell lines (CaSki, SiHa, and HeLa, HeLaS3) along with adenovirus expressing β β β β-galactosidase as a negative control. Adenovirus-delivered p53 overexpression resulted in a more significant suppression of cell growth in HPV 18-infected cells (HeLa and HeLaS3) and a lesser suppression in HPV 16-infected cells (CaSki and SiHa). However, no suppression was observed in cells infected with a negative control virus. p53 overexpression also induced apoptosis and cell cycle arrest, as determined by annexin V and propidium iodide staining. In particular, the cell cycle was arrested in the G 2 /M phase in CaSki cells. In contrast, cell cycles were arrested in the G 1 phase in HeLa cells, suggesting that the arrest phase is dependent upon the cervical cancer cell line. Taken together, these data support the idea that overexpressed p53 protein plays a differential role in suppressing cervical cancer cell growth through apoptosis and cell cycle arrest in either G 1 or G 2 /M phase, depending on the cancer cell line.

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Radiation-enhanced expression of E6/E7 transforming oncogenes of human papillomavirus-16 in human cervical carcinoma

Cited by 57 publications

References 31 publications

External Beam Radiation of Tumors Alters Phenotype of Tumor Cells to Render Them Susceptible to Vaccine-Mediated T-Cell Killing

External Beam Radiation of Tumors Alters Phenotype of Tumor Cells to Render Them Susceptible to Vaccine-Mediated T-Cell Killing

Complexes of Human Papillomavirus Type 16 E6 Proteins Form Pseudo-Death-Inducing Signaling Complex Structures during Tumor Necrosis Factor-Mediated Apoptosis

Differential Suppression of Human Cervical Cancer Cell Growth by Adenovirus Delivery of p53 in vitro: Arrest Phase of Cell Cycle Is Dependent on Cell Line

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