Enhanced StefinA and Sprr2 expression during papilloma formation in HPV8 transgenic mice

Lazić, Daliborka; Alborzi, Farnoosh; Marcuzzi, Gian Paolo; Angel, Peter; Heß, Jochen; Pfister, Herbert; Akgül, Baki

doi:10.1016/j.jdermsci.2011.02.006

Cited by 14 publications

(15 citation statements)

References 30 publications

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“…To quantify mRNA levels of cellular genes, quantitative reverse transcription (qRT)-PCR using the LightCycler system (Roche, Mannheim, Germany) was performed as described previously (46,47). Briefly, total cellular RNA was isolated with the RNeasy kit (Qiagen, Hilden, Germany) and DNase digestion was performed on a column using RNase-free DNase.…”

Section: Methodsmentioning

confidence: 99%

Expression of Betapapillomavirus Oncogenes Increases the Number of Keratinocytes with Stem Cell-Like Properties

Hufbauer

Biddle

Borgogna

et al. 2013

J Virol

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Section: Methodsmentioning

confidence: 99%

Expression of Betapapillomavirus Oncogenes Increases the Number of Keratinocytes with Stem Cell-Like Properties

Hufbauer

Biddle

Borgogna

et al. 2013

J Virol

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“…HPV5 and HPV8, both members of the beta 1 species, have been found in 90% of cutaneous squamous cell carcinoma (SCC) in EV patients. [12][13][14] These tumors resulted from HPV8 oncoprotein mediated prevention of UV-induced DNA damage repair and overriding physiological cell cycle checkpoints, thus allowing damaged cells to persist and even to replicate whilst harboring DNA lesions. Especially, immunosuppressed organ-transplant-recipients also have a higher susceptibility to betaHPV infections of the skin as well as an increased risk of developing SCC compared to healthy individuals.…”

Section: Introductionmentioning

confidence: 99%

“…11 In addition, transgenic mice expressing HPV8-CER under the control of the keratin-14 promoter (K14-HPV8-CER) developed spontaneous as well as UV-induced skin papillomas with partial dysplasia, which in approximately 6% even led to the formation of skin SCC. [12][13][14] These tumors resulted from HPV8 oncoprotein mediated prevention of UV-induced DNA damage repair and overriding physiological cell cycle checkpoints, thus allowing damaged cells to persist and even to replicate whilst harboring DNA lesions. 15,16 In addition, ataxia telangiectasia mutated (ATM) and ataxia telangiectasia and Rad3 related protein (ATR), both key proteins of the DNA damage repair pathway, are decreased in cells expressing HPV5 or HPV8 E6 proteins in a p300-dependent manner.…”

Section: Introductionmentioning

confidence: 99%

Human papillomavirus type 8 oncoproteins E6 and E7 cooperate in downregulation of the cellular checkpoint kinase‐1

Akgül

Kirschberg

Storey

et al. 2019

Intl Journal of Cancer

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Human papillomavirus 8 (HPV8) is associated with the development of squamous cell carcinoma (SCC) of the skin. HPV‐infected keratinocytes are able to override normal checkpoint control mechanisms and sustain cell cycle activity, allowing for synthesis of cellular proteins necessary for viral genome amplification. To study how HPV8 may disrupt cell cycle control, we analyzed the impact of HPV8 early gene expression on one of the key regulators of cell cycle and DNA damage response, checkpoint kinase‐1 (CHK1). We found that expression of E1, E1̂E4, E2, E6 or E7 individually did not affect CHK1; however, keratinocytes expressing the complete early genome region (CER) of HPV8 showed a profound loss of CHK1 protein levels, that proved to be mediated by E6E7 co‐expression. Neither CHK1 promoter regulation nor the ubiquitin‐proteasome pathway are involved in HPV8‐mediated CHK1 repression. However, CHK1 protein repression in organotypic skin cultures was paralleled by downregulation of the autophagy marker LC3B. Treatment of HPV8‐CER expressing cells with the autophagy inhibitor Bafilomycin A1 rescued CHK1 expression and led to LC3B accumulation. Taken together, our data implicate that CHK1 autophagic degradation is enhanced by HPV8, which may contribute to the oncogenic potential of the virus.

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“…For total RNA isolation from retrovirally transduced keratinocytes, an RNAeasy kit (Qiagen) was used and cDNA was generated as described previously (Lazić et al, 2011). The primers used for qRT-PCR were as follows: Sample measurements were performed together with a plasmid comprising the respective gene fragment, which was used to generate standard dilutions.…”

Section: Methodsmentioning

confidence: 99%

The levels of epithelial anchor proteins β-catenin and zona occludens-1 are altered by E7 of human papillomaviruses 5 and 8

Heuser

Hufbauer

Marx

et al. 2016

Journal of General Virology

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Infection with viruses of the genus Betapapillomavirus, b-human papillomaviruses (b-HPV), is implicated in the development of non-melanoma skin cancer. This was first evidenced for HPV5 and HPV8 in patients with the skin disease epidermodysplasia verruciformis (EV). The relocalization of the junctional bridging proteins b-catenin and zona occludens-1 (ZO-1) from the adherens and tight junctions are common processes of the epithelial-mesenchymal transition (EMT) associated with tumour invasion. Here, we report that b-catenin and ZO-1 are strongly upregulated by the E7 oncoproteins of HPV5 and HPV8 in keratinocytes grown in organotypic skin cultures. Although the membrane-tethered form of b-catenin was elevated, no signs of b-catenin activity within the canonical Wnt signalling pathway could be detected. The upregulation of b-catenin and ZO-1 could also be confirmed in the skin of HPV8 transgenic mice as well as in cutaneous squamous cell carcinomas of EV patients. These data provide the first evidence that b-catenin and ZO-1 are direct targets of E7 of the oncogenic b-HPV types 5 and 8. The ability to deregulate these epithelial junction proteins may contribute to the oncogenic potential of these viruses in human skin.

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Enhanced StefinA and Sprr2 expression during papilloma formation in HPV8 transgenic mice

Cited by 14 publications

References 30 publications

Expression of Betapapillomavirus Oncogenes Increases the Number of Keratinocytes with Stem Cell-Like Properties

Expression of Betapapillomavirus Oncogenes Increases the Number of Keratinocytes with Stem Cell-Like Properties

Human papillomavirus type 8 oncoproteins E6 and E7 cooperate in downregulation of the cellular checkpoint kinase‐1

The levels of epithelial anchor proteins β-catenin and zona occludens-1 are altered by E7 of human papillomaviruses 5 and 8

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