Portal de investigação
Human Papillomavirus 16-Transgenic Mice as a Model to Study Cancer-Associated Cachexia
Data de publicação:
Autores da FMUP
Participantes de fora da FMUP
- da Silva, SP
- Santos, JMO
- Mestre, VF
- Medeiros-Fonseca, B
- Oliveira, PA
- Bastos, MMSM
- da Costa, RMG
Abstract
Cancer cachexia is a multifactorial syndrome characterized by general inflammation, weight loss and muscle wasting, partly mediated by ubiquitin ligases such as atrogin-1, encoded byFbxo32. Cancers induced by high-risk human papillomavirus (HPV) include anogenital cancers and some head-and-neck cancers and are often associated with cachexia. The aim of this study was to assess the presence of cancer cachexia in HPV16-transgenic mice with or without exposure to the chemical carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). Male mice expressing the HPV16 early region under the control of the cytokeratin 14 gene promoter (K14-HPV16; HPV+) and matched wild-type mice (HPV-) received DMBA (or vehicle) topically over 17 weeks of the experiment. Food intake and body weight were assessed weekly. The gastrocnemius weights andFbxo32expression levels were quantified at sacrifice time. HPV-16-associated lesions in different anatomic regions were classified histologically. Although unexposed HPV(+)mice showed higher food intake than wild-type matched group (p < 0.01), they presented lower body weights (p < 0.05). This body weight trend was more pronounced when comparing DMBA-exposed groups (p < 0.01). The same pattern was observed in the gastrocnemius weights (between the unexposed groups:p < 0.05; between the exposed groups:p < 0.001). Importantly, DMBA reduced body and gastrocnemius weights (p < 0.01) when comparing the HPV(+)groups. Moreover, theFbxo32gene was overexpressed in DMBA-exposed HPV(+)compared to control mice (p< 0.05). These results show that K14-HPV16 mice closely reproduce the anatomic and molecular changes associated with cancer cachexia and may be a good model for preclinical studies concerning the pathogenesis of this syndrome.
Dados da publicação
- ISSN/ISSNe:
- 1661-6596, 1661-6596
- Tipo:
- Article
- Páginas:
- -
- DOI:
- 10.3390/ijms21145020
International Journal of Molecular Sciences Multidisciplinary Digital Publishing Institute (MDPI)
Citações Recebidas na Web of Science: 4
Documentos
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Filiações
Keywords
- cancer cachexia; HPV16; K14-HPV16; mouse model; DMBA; wasting syndrome
Financiamento
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Citar a publicação
da SP,Santos J,Mestre VF,Medeiros B,Oliveira PA,Bastos MMSM,da RMG,Medeiros R. Human Papillomavirus 16-Transgenic Mice as a Model to Study Cancer-Associated Cachexia. Int. J. Mol. Sci. 2020. 21. (14):5020. IF:5,923. (1).
