Skin tumor formation in human papillomavirus 8 transgenic mice is associated with a deregulation of oncogenic miRNAs and their tumor suppressive targets

Hufbauer, Martin; Lazić, Daliborka; Reinartz, Markus; Akgül, Baki; Pfister, Herbert; Weissenborn, Soenke J.

doi:10.1016/j.jdermsci.2011.06.008

Cited by 30 publications

(29 citation statements)

References 51 publications

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“…In the DMBA/TPA model tumor formation is mainly driven by mutations in the ha-ras proto-oncogene that are induced by DMBA (24,25), whereas HPV8 induces tumor formation via its own oncogenic proteins, in particular E6 (22,32). This involves microRNA-mediated downregulation of the tumor suppressors RB and PTEN (33). In contrast, ras mutations are rarely found in these tumors (22,32).…”

Section: Discussionmentioning

confidence: 99%

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

et al. 2013

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The antioxidant enzyme peroxiredoxin 6 (Prdx6) is a key regulator of the cellular redox balance, particularly under stress conditions. We identified Prdx6 as an important player in different phases of skin carcinogenesis. Loss of Prdx6 in mice enhanced the susceptibility to skin tumorigenesis, whereas overexpression of Prdx6 in keratinocytes of transgenic mice had the opposite effect. The tumor-preventive effect of Prdx6, which was observed in a human papilloma virus 8-induced and a chemically induced tumor model, was not due to alterations in keratinocyte proliferation, apoptosis, or in the inflammatory response. Rather, endogenous and overexpressed Prdx6 reduced oxidative stress as reflected by the lower levels of oxidized phospholipids in the protumorigenic skin of Prdx6 transgenic mice and the higher levels in Prdx6-knockout mice than in control animals. In contrast to its beneficial effect in tumor prevention, overexpression of Prdx6 led to an acceleration of malignant progression of existing tumors, revealing a dual function of this enzyme in the pathogenesis of skin cancer. Finally, we found strong expression of PRDX6 in keratinocytes of normal human skin and in the tumor cells of squamous cell carcinomas, indicating a role of Prdx6 in human skin carcinogenesis. Taken together, our data point to the potential usefulness of Prdx6 activators or inhibitors for controlling different stages of skin carcinogenesis. Cancer Res; 73(11); 3460-9. Ó2013 AACR.

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Section: Discussionmentioning

confidence: 99%

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

et al. 2013

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“…Reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and tissue inhibitor of metalloproteinase 3 (Timp3), which are both tumor suppressors and inhibitors of matrix metalloproteinases (MMPs), as well as tumor suppressor programmed cell death 4 (PDCD4) and tropomyosin 1 (TPM1) have been shown to be downregulated by hsa-miR-21 [26][27][28]. RECK and Timp3 downregulation has also been shown in squamous cell lung cancer, and there is evidence for PDCD4 down-regulation in cSCC in a transgenic mouse model and for hsa-miR-21 mediated TPM1 down-regulation in tongue SCC [9,27,29,30]. This preliminary evidence suggests that it would be interesting to investigate whether hsa-miR-21 induced down-regulation of RECK, Timp3, PDCD4 or TPM1 could be confirmed in cSCC.…”

Section: Discussionmentioning

confidence: 99%

Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma

Sand

Skrygan

Georgas

et al. 2012

Journal of Dermatological Science

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“…For hrHPV types in the alphapapillomavirus group, extensive in vitro studies and transgenic animal models have confirmed the oncogenic potential of E6 and E7 proteins 96979899100101. Oncogenic activities of the E6 and E7 proteins includes p53 sequestration, pRB binding, interference with DNA damage response pathways, disruption of cell cycle and cell division pathways, and immune evasion (reviewed in 551102).…”

Section: Pathology/symptomatologymentioning

confidence: 99%

HPV disease transmission protection and control

Christensen¹

2016

MIC

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Human papillomaviruses (HPVs) represent a large collection of viral types associated with significant clinical disease of cutaneous and mucosal epithelium. HPV-associated cancers are found in anogenital and oral mucosa, and at various cutaneous sites. Papillomaviruses are highly species and tissue restricted, and these viruses display both mucosotropic, cutaneotropic or dual tropism for epithelial tissues. A subset of HPV types, predominantly mucosal, are also oncogenic and cancers with these HPV types account for more than 200,000 deaths world-wide. Host control of HPV infections requires both innate and adaptive immunity, but the viruses have developed strategies to escape immune detection. Viral proteins can disrupt both innate pathogen-sensing pathways and T-cell based recognition and subsequent destruction of infected tissues. Current treatments to manage HPV infections include mostly ablative strategies in which recurrences are common and only active disease is treated. Although much is known about the papillomavirus life cycle, viral protein functions, and immune responsiveness, we still lack knowledge in a number of key areas of PV biology including tissue tropism, site-specific cancer progression, codon usage profiles, and what are the best strategies to mount an effective immune response to the carcinogenic stages of PV disease. In this review, disease transmission, protection and control are discussed together with questions related to areas in PV biology that will continue to provide productive opportunities of discovery and to further our understanding of this diverse set of human viral pathogens.

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Skin tumor formation in human papillomavirus 8 transgenic mice is associated with a deregulation of oncogenic miRNAs and their tumor suppressive targets

Cited by 30 publications

References 51 publications

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

Dual Role of the Antioxidant Enzyme Peroxiredoxin 6 in Skin Carcinogenesis

Microarray analysis of microRNA expression in cutaneous squamous cell carcinoma

HPV disease transmission protection and control

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