Clinical Observations, Virologic Studies, and Treatment Trials in Patients with Epidermodysplasia Verruciformis, a Disease Induced by Specific Human Papillomaviruses

Lutzner, Marvin A.; Blanchet-Bardon, C; Orth, Gérard

doi:10.1038/jid.1984.15

Cited by 126 publications

(109 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…These studies suggest a mechanism by which carcinogenesis may result from UV activation of the papilloma virus DNA sequences, or cooperation between the effects of the papilloma virus DNA gene products and a separate change induced by UV radiation to induce the neoplastic state. It is interesting to note that human papilloma viral DNA sequences have been detected in hyperkeratotic lesions from sun-damaged skin (Spradbrow et al, 1983), in KA and malignant melanoma (Scheurlen et al, 1986), in patients with epidermodysplasia verruciformis (Lutzner et al, 1984;Orth et al, 1979) and in immunosuppressed patients (Lutzner et al, 1980). Further, progression to malignancy in epidermodysplasia patients occurred only in the lesions on sun-exposed body sites.…”

Section: Cooperation Between Oncogenesmentioning

confidence: 99%

Molecular Mechanisms of Ultraviolet Radiation Carcinogenesis

Ananthaswamy

Pierceall

1990

Photochem & Photobiology

358

198

View full text Add to dashboard Cite

Section: Cooperation Between Oncogenesmentioning

confidence: 99%

Molecular Mechanisms of Ultraviolet Radiation Carcinogenesis

Ananthaswamy

Pierceall

1990

Photochem & Photobiology

358

198

View full text Add to dashboard Cite

“…The association between beta-HPVs and skin cancer was first identified in patients with the rare inherited disorder epidermodysplasia verruciformis (EV) (27). These individuals have a predisposition to the early development of disseminated, persistent flat warts and macular lesions following infection with a specific group of about 20 related beta-HPV genotypes, also known as EV types.…”

mentioning

confidence: 99%

E6 Proteins from Multiple Human Betapapillomavirus Types Degrade Bak and Protect Keratinocytes from Apoptosis after UVB Irradiation

Underbrink

Howie

Bedard

et al. 2008

J Virol

147

157

View full text Add to dashboard Cite

Human papillomavirus (HPV) types from the beta genus (beta-HPVs) have been implicated in the development of skin cancer. A potentially important aspect of their carcinogenic role is the ability of the E6 protein to degrade the proapoptotic family member Bak, which gives cells the ability to survive UV damage. However, it is unknown if the ability to degrade Bak is limited to certain beta-HPV types or whether E6 expression in keratinocytes affects other proteins important for apoptosis signaling. We tested the abilities of E6 proteins from several representative members of the beta-HPVs to degrade Bak and protect UV-treated keratinocytes from apoptosis. The E6 proteins of the beta-HPV type 5 (HPV5), -8, -20, -22, -38, -76, -92, and -96, as well as the alpha genus HPV HPV16, all degraded Bak or prevented its accumulation following UV treatment but did not degrade Bak constitutively. In addition, when tested using HPV16 E6 (16E6) and 8E6 as representative E6 proteins from the alpha and beta genera, respectively, Bak degradation was dependent on the E3 ubiquitin ligase, E6AP. Other important regulators of apoptotic signaling were examined and found to be unperturbed by the expression of the beta-HPV E6 proteins. Importantly, the expression of beta-HPV E6 proteins protected keratinocytes from apoptosis to the same extent as 16E6-expressing cells. In conclusion, several of the beta-HPV types possess the ability to protect UV-treated keratinocytes from apoptosis by reducing levels of Bak in those cells, thus blocking the intrinsic apoptotic pathway.Human papillomaviruses (HPVs) are small DNA tumor viruses that infect cutaneous and mucosal epithelia and disseminate by replication in terminally differentiated keratinocytes. So far, over 100 different types have been identified and characterized on the basis of DNA sequence analysis (12). Only a small number of these display a strong association with cancer development. Most notably, the high-risk types (16, 18, 31, 33, etc.) of alpha genus HPVs (alpha-HPVs) play a critical role in the development of cervical cancer. These same types have also been implicated in the majority of other anogenital cancers and a subset of head and neck carcinomas (11,43).Recently, the beta-HPVs, which cause cutaneous lesions in humans, have been linked to the development of skin cancers (32). The association between beta-HPVs and skin cancer was first identified in patients with the rare inherited disorder epidermodysplasia verruciformis (EV) (27). These individuals have a predisposition to the early development of disseminated, persistent flat warts and macular lesions following infection with a specific group of about 20 related beta-HPV genotypes, also known as EV types. About half of EV patients develop premalignant skin lesions and squamous cell carcinomas by age 40, primarily in sun-exposed areas (30). DNA from these lesions was found to harbor HPV genomes, suggesting a cocarcinogenic role of beta-HPVs and UV radiation in the early development of EV cancers (32). By use of sensitive P...

show abstract

“…Furthermore, specific diseases are associated with specific HPVs (17,22,26,28). For example, HPVs 16 and 18 are preferentially associated with human cervical and oral carcinomas (3,8,47,48).…”

mentioning

confidence: 99%

Differential early viral gene expression in two stages of human papillomavirus type 16 DNA-induced malignant transformation.

Yasumoto¹,

Doniger²,

DiPaolo³

1987

Mol. Cell. Biol.

View full text Add to dashboard Cite

Human papiflomavirus (HPV) (6,11,34). Furthermore, specific diseases are associated with specific HPVs (17,22,26,28). For example, HPVs 16 and 18 are preferentially associated with human cervical and oral carcinomas (3,8,47,48). Analysis of cancer biopsies and some cell lines derived from human cervical carcinoma has demonstrated that integrated HPV 16 and 18 DNAs expressed transcriptional activity (10,20,35,47); specific transcripts have been mapped to the E6-E7 and El early gene regions (33,35,38,47). In a few cases, however, viral DNA was not detected in tumor cells (20,47) (Fig. 1); the pBR322 poison sequences (21) are absent in pdMMTneo.Transfection. The transfection procedure previously described (45) was modified; 2 to 5 ,ug of plasmid DNA for 1 x 105 to 5 x 105 NIH 3T3 cells was transfected without carrier DNA. Metals in the medium were sufficient to induce the mouse methallothionein promotor. For the focus-forming assay, transfected NIH 3T3 cells were maintained by refeeding in Dulbecco modified minimal essential medium supplemented with 10% bovine calf serum (GIBCO Laboratories). Cell lines derived from morphologically transformed foci were designated PM3T3Fo. A portion of the transfectants was selected with 400 ,g of G418 (GIBCO) per ml 10 to 14 days after transfection, and individual G418-resistant colonies were isolated. After selection and isolation, these lines (PM3T3G°) were expanded and grown without added G418.RNA extraction and enrichment of poly(A)-terminated mRNA. Subconfluent cultured cells were lysed with a 6 M guanidine thiocyanate solution containing 5 mM sodium citrate, 0.5% sodium sarcosyl, and 0.1 M ,B-mercaptoethanol. After high-molecular-weight cellular DNA was sheared by passing the lysate through a 20-gauge needle several times, the lysate was overlaid on a 6.1 M (1.52-g/ml) cesium trifluoroacetate cushion and centrifuged in an SW27 rotor at 25,000 rpm for 16 h at 15°C. Pelleted RNA was washed with 5 ml of 70% ethanol, dried, and dissolved in 1 ml of distilled water. After ethanol precipitation, RNA was redissolved in H20 and stored at -70°C. Poly(A)-terminated mRNA was 2165 on May 8, 2018 by guest

show abstract

Clinical Observations, Virologic Studies, and Treatment Trials in Patients with Epidermodysplasia Verruciformis, a Disease Induced by Specific Human Papillomaviruses

Cited by 126 publications

References 41 publications

Molecular Mechanisms of Ultraviolet Radiation Carcinogenesis

Molecular Mechanisms of Ultraviolet Radiation Carcinogenesis

E6 Proteins from Multiple Human Betapapillomavirus Types Degrade Bak and Protect Keratinocytes from Apoptosis after UVB Irradiation

Differential early viral gene expression in two stages of human papillomavirus type 16 DNA-induced malignant transformation.

Contact Info

Product

Resources

About