دورية أكاديمية
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HPV16 induces penile intraepithelial neoplasia and squamous cell carcinoma in transgenic mice: first mouse model for HPV-related penile cancer.

التفاصيل البيبلوغرافية
العنوان: HPV16 induces penile intraepithelial neoplasia and squamous cell carcinoma in transgenic mice: first mouse model for HPV-related penile cancer.
المؤلفون: Medeiros-Fonseca B; CITAB, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal., Mestre VF; CITAB, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal., Estêvão D; Grupo de Oncologia Molecular e Patologia Viral, CI-IPOP, IPO-Porto, Porto, Portugal.; Faculdade de Medicina, Universidade do Porto, Porto, Portugal., Sánchez DF; Instituto de Patología e Investigación and Universidad Nacional de Asunción, Asunción, Paraguay., Cañete-Portillo S; Instituto de Patología e Investigación and Universidad Nacional de Asunción, Asunción, Paraguay., Fernández-Nestosa MJ; Instituto de Patología e Investigación and Universidad Nacional de Asunción, Asunción, Paraguay., Casaca F; Botelho Moniz Análises Clínicas (BMAC), Porto, Portugal., Silva S; Botelho Moniz Análises Clínicas (BMAC), Porto, Portugal., Brito H; Biobanco de Tumores e DNA do Maranhão, PPGSAD, Universidade Federal do Maranhão (UFMA), São Luís, Brazil., Félix A; Nova Medical School, Universidade Nova de Lisboa, Lisbon, Portugal.; Serviço de Anatomia Patológica, IPO-Lisboa, Lisbon, Portugal., Medeiros R; Grupo de Oncologia Molecular e Patologia Viral, CI-IPOP, IPO-Porto, Porto, Portugal.; Faculdade de Medicina, Universidade do Porto, Porto, Portugal.; Serviço de Virologia, IPO-Porto, Porto, Portugal.; Liga Portuguesa Contra o Cancro - Núcleo Regional do Norte, Porto, Portugal.; CEBIMED, Faculdade de Ciências da Saúde, Universidade Fernando Pessoa, Porto, Portugal., Colaço B; CITAB, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal.; Departamento de Zootecnia, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal., Oliveira PA; CITAB, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal.; Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal., Bastos MM; LEPABE, Faculdade de Engenharia, Universidade do Porto, Porto, Portugal., Nelson PS; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.; University of Washington, Seattle, WA, USA., Vakar-Lopez F; LEPABE, Faculdade de Engenharia, Universidade do Porto, Porto, Portugal., Gaivão I; CECAV and Department of Genetics and Biotechnology, University of Trás-os-Montes and Alto Douro (UTAD), Vila Real, Portugal., Brito L; Biobanco de Tumores e DNA do Maranhão, PPGSAD, Universidade Federal do Maranhão (UFMA), São Luís, Brazil., Lopes C; Botelho Moniz Análises Clínicas (BMAC), Porto, Portugal.; Grupo de Patologia Experimental, Ci-IPOP, IPO-Porto, Porto, Portugal.; Departamento de Patologia e Imunologia Molecular, ICBAS, Universidade do Porto, Porto, Portugal., Cubilla AL; Instituto de Patología e Investigación and Universidad Nacional de Asunción, Asunción, Paraguay., Gil da Costa RM; CITAB, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal.; Grupo de Oncologia Molecular e Patologia Viral, CI-IPOP, IPO-Porto, Porto, Portugal.; Biobanco de Tumores e DNA do Maranhão, PPGSAD, Universidade Federal do Maranhão (UFMA), São Luís, Brazil.; LEPABE, Faculdade de Engenharia, Universidade do Porto, Porto, Portugal.; Human Biology Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
المصدر: The Journal of pathology [J Pathol] 2020 Aug; Vol. 251 (4), pp. 411-419.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: John Wiley And Sons Country of Publication: England NLM ID: 0204634 Publication Model: Print Cited Medium: Internet ISSN: 1096-9896 (Electronic) Linking ISSN: 00223417 NLM ISO Abbreviation: J Pathol Subsets: MEDLINE
أسماء مطبوعة: Publication: Chichester : John Wiley And Sons
Original Publication: London, Oliver & Boyd.
مواضيع طبية MeSH: Carcinoma in Situ/*virology , Carcinoma, Squamous Cell/*virology , Human papillomavirus 16/*physiology , Papillomavirus Infections/*virology , Penile Neoplasms/*virology, Animals ; Carcinogenesis ; Carcinoma in Situ/pathology ; Carcinoma, Squamous Cell/pathology ; Cell Proliferation ; Disease Models, Animal ; Human papillomavirus 16/genetics ; Humans ; Immunohistochemistry ; Male ; Mice ; Mice, Transgenic ; Oncogene Proteins, Viral/genetics ; Oncogene Proteins, Viral/metabolism ; Papillomavirus E7 Proteins/genetics ; Papillomavirus E7 Proteins/metabolism ; Papillomavirus Infections/pathology ; Penile Neoplasms/pathology ; Penis/pathology ; Penis/virology ; Random Allocation ; Repressor Proteins/genetics ; Repressor Proteins/metabolism
مستخلص: Penile cancer is an under-studied disease that occurs more commonly in developing countries and 30-50% of cases show high-risk human papillomavirus (HPV) infection. Therapeutic advances are slow, largely due to the absence of animal models for translational research. Here, we report the first mouse model for HPV-related penile cancer. Ten-week-old mice expressing all the HPV16 early genes under control of the cytokeratin 14 (Krt14) gene promoter and matched wild-type controls were exposed topically to dimethylbenz(a)anthracene (DMBA) or vehicle for 16 weeks. At 30 weeks of age, mice were sacrificed for histological analysis. Expression of Ki67, cytokeratin 14, and of the HPV16 oncogenes E6 and E7 was confirmed using immunohistochemistry and quantitative PCR, respectively. HPV16-transgenic mice developed intraepithelial lesions including condylomas and penile intraepithelial neoplasia (PeIN). Lesions expressed cytokeratin 14 and the HPV16 oncogenes E6 and E7 and showed deregulated cell proliferation, demonstrated by Ki67-positive supra-basal cells. HPV16-transgenic mice exposed to DMBA showed increased PeIN incidence and squamous cell carcinoma. Malignant lesions showed varied histological features closely resembling those of HPV-associated human penile cancers. Wild-type mice showed no malignant or pre-malignant lesions even when exposed to DMBA. These observations provide the first experimental evidence to support the etiological role of HPV16 in penile carcinogenesis. Importantly, this is the first mouse model to recapitulate key steps of HPV-related penile carcinogenesis and to reproduce morphological and molecular features of human penile cancer, providing a unique in vivo tool for studying its biology and advancing basic and translational research. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
(© 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)
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فهرسة مساهمة: Keywords: HPV; PeIN; carcinogenesis; condyloma; mouse model; penile cancer
المشرفين على المادة: 0 (E6 protein, Human papillomavirus type 16)
0 (Oncogene Proteins, Viral)
0 (Papillomavirus E7 Proteins)
0 (Repressor Proteins)
0 (oncogene protein E7, Human papillomavirus type 16)
تواريخ الأحداث: Date Created: 20200604 Date Completed: 20201217 Latest Revision: 20201217
رمز التحديث: 20231215
DOI: 10.1002/path.5475
PMID: 32488868
قاعدة البيانات: MEDLINE
الوصف
تدمد:1096-9896
DOI:10.1002/path.5475