Differences in transcriptional activity of cutaneous human papillomaviruses

Vasiljević, Nataša; Nielsen, Lone; Doherty, Geoff; Dillner, Joakim; Forslund, Ola; Norrild, Bodil

doi:10.1016/j.virusres.2008.07.013

Cited by 4 publications

(4 citation statements)

References 39 publications

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“…Our analysis of acquired seropositivity and lost seropositivity in relation to SCC risk are consistent with chance findings, although we note that the types with marginally significant associations (HPV 38 and 8) have transforming characteristics (29,30,31,32) and that some (but not all ( 9)) previous studies have also suggested an NMSC association (12).…”

Section: Discussionsupporting

confidence: 90%

Prospective Study of Human Papillomavirus Seropositivity and Risk of Nonmelanoma Skin Cancer

Andersson¹,

Michael²,

Luostarinen³

et al. 2012

American Journal of Epidemiology

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Cutaneous human papillomaviruses (HPVs) have been associated with squamous cell carcinoma (SCC) in case-control studies, but there are limited data from prospective studies assessing whether virus exposure predicts risk of future cancer development. Two major biobanks, the Southern Sweden Microbiology Biobank (1971-2003) and the Janus Biobank (1973-2003) in Norway, containing samples from 850,000 donors, were searched for incident skin cancer for up to 30 years using registry linkages. Altogether, 2,623 donors with samples taken before diagnosis of SCC or basal cell carcinoma (BCC) of the skin were identified. Prediagnostic samples and samples from 2,623 matched controls were tested for antibodies against 33 types of HPV. Baseline seropositivity to HPV types in genus β species 2 was associated with SCC risk (odds ratio = 1.3, 95% confidence interval: 1.1, 1.7); this was also the case for samples taken more than 18 years before diagnosis (odds ratio = 1.8, 95% confidence interval: 1.1, 2.8). Type-specific persistent seropositivity entailed elevated point estimates for SCC risk for 29 HPV types and decreased point estimates for only 3 types. After multiple hypothesis adjustment, HPV 76 was significantly associated with SCC risk and HPV 9 with BCC risk. In summary, seropositivity for certain HPV types was associated with an increased risk for future development of SCC and BCC.

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Section: Discussionsupporting

confidence: 90%

Prospective Study of Human Papillomavirus Seropositivity and Risk of Nonmelanoma Skin Cancer

Andersson¹,

Michael²,

Luostarinen³

et al. 2012

American Journal of Epidemiology

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“…We have previously demonstrated that the activation or suppression of a number of cutaneous HPV promoters by UV-irradiation is type specific rather than genus- or species-specific [39]. This was recently confirmed by others [36]. Chronic exposure of HPV20- and HPV27E6/E7 transgenic mice to UV-irradiation resulted in the formation of papillomas and malignant lesions of the skin [58].…”

Section: Discussionsupporting

confidence: 56%

“…E6 gene expression of several cutaneous HPV types protected keratinocytes from UV-B induced apoptosis [34]–[36] by mediating degradation [34] or a reduction in the levels of pro-apoptotic Bak [37] and thereby preventing the release of pro-apoptotic factors from mitochondria [38]. We demonstrated that p53-mediated caspase-dependent degradation of HPV20E6 was rescued by mutant p53R248W and ΔNp63α and other unknown proteins involved in proteasome degradation [13].…”

Section: Introductionmentioning

confidence: 82%

“…We demonstrated that p53-mediated caspase-dependent degradation of HPV20E6 was rescued by mutant p53R248W and ΔNp63α and other unknown proteins involved in proteasome degradation [13]. We now investigated whether similar interactions between mutant p53R248W, wtp53 and ΔNp63α with E6 of other cutaneous HPV types occurred, as we had previously demonstrated a type specific, rather than genus- or species-specific UV-induced activation or suppression of a number of cutaneous HPV promoters [36], [39]. The present study demonstrates a differential regulation of the E6 genes of cutaneous types HPV4, HPV5, HPV7, HPV27, HPV38, HPV48, HPV60 and HPV77 by wtp53.…”

Section: Introductionmentioning

confidence: 87%

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Differential Regulation of Cutaneous Oncoprotein HPVE6 by wtp53, Mutant p53R248W and ΔNp63α is HPV Type Dependent

Fei

Villiers

2012

PLoS ONE

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UV exposure and p53 mutations are major factors in non-melanoma skin cancer, whereas a role for HPV infections has not been defined. Previous data demonstrated the wtp53-mediated degradation of cutaneous HPV20E6 by caspase-3. ΔNp63α and hot-spot mutant p53R248W conveyed a protective effect on HPV20E6 under these conditions. We demonstrate a differential regulation by wtp53 of the E6 genes of cutaneous types HPV4, HPV5, HPV7, HPV27, HPV38, HPV48, HPV60 and HPV77. Caspase- or proteasome-mediated down-regulation was HPV type dependent. Mutant p53R248W up-regulated expression of all these E6 proteins as did ΔNp63α except for HPV38E6 which was down-regulated by the latter. None of these cellular proteins affected HPV41E6 expression. Ectopic expression of both mutp53R248W and ΔNp63α in the normal NIKS keratinocyte cell line harbouring endogenous p53 and p63however led to a down-regulation of HPV20E6. We demonstrate that HPV20E6 expression in these cells is modulated by additional, yet unidentified, cellular protein(s), which are not necessarily involved in apoptosis or autophagy. We further demonstrate proliferation of HPV20E6-expressing keratinocytes. Levels of proteins involved in cell cycle control, cyclin-D1, cdk6 and p16INK4a, phosphorylated pRB, as well as c-Jun and p-c-Jun, were all increased in these cells. HPV20E6 did not compete for the interaction between p16INK4a with cyclin-D1 or cdk6. Phosphorylation of pRB in the HPV20E6 expressing cells seems to be sufficient to override the cytokenetic block induced by the p16INK4a/pRB pathway. The present study demonstrates the diverse influence of p53 family members on individual cutaneous HPVE6 proteins. HPV20E6 expression also resulted in varying protein levels of factors involved in proliferation and differentiation.

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Activities of E7 promoters in the human papillomavirus type 16 genome during cell differentiation

2010

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Differences in transcriptional activity of cutaneous human papillomaviruses

Cited by 4 publications

References 39 publications

Prospective Study of Human Papillomavirus Seropositivity and Risk of Nonmelanoma Skin Cancer

Prospective Study of Human Papillomavirus Seropositivity and Risk of Nonmelanoma Skin Cancer

Differential Regulation of Cutaneous Oncoprotein HPVE6 by wtp53, Mutant p53R248W and ΔNp63α is HPV Type Dependent

Activities of E7 promoters in the human papillomavirus type 16 genome during cell differentiation

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