Human papillomavirus E6 and E7 oncoproteins alter cell cycle progression but not radiosensitivity of carcinoma cells treated with low-dose-rate radiation

DeWeese, Theodore L.; Walsh, Jared P.; Dillehay, Larry E.; Kessis, Theodore D.; Hedrick, Lora; Cho, Kathleen R.; Nelson, William G.

doi:10.1016/s0360-3016(96)00448-8

Cited by 65 publications

(39 citation statements)

References 50 publications

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“…[12][13][14]17,18,40,45,51 The reason for the improved survival is unclear; however, improved radiation responsiveness, immune surveillance to viral antigens, and the absence of field cancerization in these patients who tend to be nonsmokers, have been postulated. 28,35,79,80 In addition, E6-related degradation of p53 in HPV-positive cancers may be functionally inequivalent to HPV-negative p53 mutations, 81,82 and therefore, HPVpositive tumors may have an intact apoptotic response to radiation and chemotherapy. 79,83 Possible therapeutic implications of an HPV-positive diagnosis are an active area of investigation.…”

Section: Clinical Significance Of An Hpv-positive Tumormentioning

confidence: 99%

“…28,35,79,80 In addition, E6-related degradation of p53 in HPV-positive cancers may be functionally inequivalent to HPV-negative p53 mutations, 81,82 and therefore, HPVpositive tumors may have an intact apoptotic response to radiation and chemotherapy. 79,83 Possible therapeutic implications of an HPV-positive diagnosis are an active area of investigation. This includes selection of patients for organ preservation therapy, which may be more successful in patients with HPV-HNSCC.…”

Section: Clinical Significance Of An Hpv-positive Tumormentioning

confidence: 99%

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Clinical Implications of Human Papillomavirus in Head and Neck Cancers

Fakhry

Gillison

2006

JCO

437

329

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Human papillomavirus (HPV) is now recognized to play a role in the pathogenesis of a subset of head and neck squamous cell carcinomas (HNSCCs), particularly those that arise from the lingual and palatine tonsils within the oropharynx. High-risk HPV16 is identified in the overwhelming majority of HPV-positive tumors, which have molecular-genetic alterations indicative of viral oncogene function. Measures of HPV exposure, including sexual behaviors, seropositivity to HPV16, and oral, high-risk HPV infection, are associated with increased risk for oropharyngeal cancer. HPV infection may be altering the demographics of HNSCC patients, as these patients tend to be younger, nonsmokers, and nondrinkers. There is sufficient evidence to conclude that a diagnosis of HPV-positive HNSCC has significant prognostic implications; these patients have at least half the risk of death from HNSCC when compared with the HPV-negative patient. The HPV etiology of these tumors may have future clinical implications for the diagnosis, therapy, screening, and prevention of HNSCC.

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Section: Clinical Significance Of An Hpv-positive Tumormentioning

confidence: 99%

Section: Clinical Significance Of An Hpv-positive Tumormentioning

confidence: 99%

Clinical Implications of Human Papillomavirus in Head and Neck Cancers

Fakhry

Gillison

2006

JCO

437

329

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“…Therefore any radiation damage would not be sufficiently repaired, and damaged cells would be more likely to die during mitosis as they progress through the cell cycle. E6 has previously been shown to sensitize mammary epithelial cells, fibroblasts and keratinocytes to chemically induced death (Xu, Meikrantz et al 1995, Hawkins, Demers et al 1996, Liu, McKalip et al 2000, Liu, Zhao et al 2007), but has been reported to have the opposite effect or no effect in other cell types exposed to ionizing radiation or DNA-damaging chemicals (DeWeese, Walsh et al 1997, Hampson, El Hady et al 2001, Shai, Nguyen et al 2007). Thus, the radiosensitizing effect might be specific to a few cell types, including keratinocytes, the natural hosts for HPVs, and be dependent on the E6*I isoform.…”

Section: Discussionmentioning

confidence: 98%

The Effect of Human Papillomavirus E6 Oncogene on the Radiosensitivity of Non-Oropharyngeal Cancer Cells

Hong¹,

Zhang²,

Zhang³

et al. 2017

CCO

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Background:We have previously shown that stable transfection of the human papillomavirus (HPV) E6*I oncogene can sensitize two HPV negative oropharyngeal cancer (OSCC) cell lines to radiation. In the current study, we extended our work on OSCC to determine whether the HPV E6 oncogene can enhance the radiosensitivity of non-OSCC cell lines. Methods:Three non-OSCC cell lines (melanoma, colorectal adenocarcinoma and large cell lung cancer) were stably transfection with the HPV E6 oncogene (E6 total, E6*I and E6*II) and treated with different doses of radiation. Clonogenic assays were used to measure the radiation survival. Results:Following transfection, there was a reduction in the survival of the melanoma cell line after 2 Gy (SF2) from 0.401 (untransfected) to 0.219 (Melanoma-E6 total). This reduction was not evident at higher doses of radiation. There was no significant change in the SF2 of melanoma-E6*I (0.303) and melanoma-E6*II (0.414). The SF2 colorectal adenocarcinoma and large cell lung cancer cell lines did not change significantly after transfection. Conclusions:The radiosensitizing effect of HPV E6 oncogene is cell line specific. We found no clear evidence of a radiosensitising effect of E6 in these three non-OSCC cancer cell lines.

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“…In response to radiation-induced DNA damage, wild-type p53 causes apoptosis and has been shown to play an important role in the radiosensitivity process [25]. Following p53 degradation by E6 in HPV-positive tumors, increased radiosensitivity was detected because of the intact apoptotic response to radiation and chemotherapy [26,27]. These findings require further validation.…”

Section: Prognosis and Biomarkersmentioning

confidence: 99%