دورية أكاديمية
HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice.
| العنوان: | HPV16 is sufficient to induce squamous cell carcinoma specifically in the tongue base in transgenic mice. |
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| المؤلفون: | Mestre VF; CITAB, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal., Medeiros-Fonseca B; 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., Casaca F; Botelho Moniz Análises Clínicas (BMAC), Porto, Portugal., Silva S; Botelho Moniz Análises Clínicas (BMAC), Porto, Portugal., Félix A; Nova Medical School, Universidade Nova de Lisboa, Lisbon, Portugal.; Serviço de Anatomia Patológica, IPO-Lisboa, Lisbon, Portugal., Silva F; Nova Medical School, Universidade Nova de Lisboa, Lisbon, 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., Seixas F; Departamento de Ciências Veterinárias, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal.; CECAV, Universidade de Trás-os-Montes e Alto Douro, UTAD, Vila Real, Portugal., Bastos MM; LEPABE, Faculdade de Engenharia, Universidade do Porto, Porto, Portugal., 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., 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., 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., 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.; LEPABE, Faculdade de Engenharia, Universidade do Porto, Porto, Portugal.; PPGSAD, Universidade Federal do Maranhão (UFMA), São Luís, Brazil. |
| المصدر: | The Journal of pathology [J Pathol] 2020 May; Vol. 251 (1), pp. 4-11. Date of Electronic Publication: 2020 Mar 10. |
| نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; 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-Electronic 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, Squamous Cell/*virology , Head and Neck Neoplasms/*virology , Human papillomavirus 16/*genetics , Papillomaviridae/*genetics, Animals ; Biomarkers, Tumor/metabolism ; Carcinoma, Squamous Cell/pathology ; Cyclin-Dependent Kinase Inhibitor p16/metabolism ; DNA, Viral/genetics ; Female ; Head and Neck Neoplasms/pathology ; Mice, Transgenic ; Papillomavirus Infections/virology |
| مستخلص: | Head and neck squamous cell carcinomas (HNSCCs) associated with human papillomavirus (HPV) occur specifically in the tonsils and the tongue base, but the reasons for this specificity remain unknown. We studied the distribution of oral and pharyngeal lesions in HPV16-transgenic mice where the expression of all the HPV16 early genes is targeted to keratinising squamous epithelia by the cytokeratin 14 (Krt14) gene promoter. At 30 weeks of age, 100% of mice developed low- and high-grade intraepithelial dysplasia at multiple sites. Twenty per cent of animals developed invasive cancers that remarkably were restricted to the tongue base, in association with the circumvallate papilla. The lesions maintained expression of CK14 (KRT14) and the HPV16 E6 and E7 oncogenes, and displayed deregulated cell proliferation and up-regulation of p16 INK4A . Malignant lesions were poorly differentiated and destroyed the tongue musculature. We hypothesised that the tongue base area might contain a transformation zone similar to those observed in the cervix and anus, explaining why HPV-positive cancers target that area specifically. Immunohistochemistry for two transformation zone markers, CK7 (KRT7) and p63 (TP63), revealed a squamocolumnar junction in the terminal duct of von Ebner's gland, composed of CK7 + luminal cells and p63 + basal cells. Dysplastic and invasive lesions retained diffuse p63 expression but only scattered positivity for CK7. Site-specific HPV-induced carcinogenesis in the tongue base may be explained by the presence of a transformation zone in the circumvallate papilla. This mouse model reproduces key morphological and molecular features of HPV-positive HNSCC, providing a unique in vivo tool for 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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| معلومات مُعتمدة: | P30 CA015704 United States CA NCI NIH HHS |
| فهرسة مساهمة: | Keywords: CK7; HNSCC; HPV; mouse model; p63; squamocolumnar junction |
| المشرفين على المادة: | 0 (Biomarkers, Tumor) 0 (Cyclin-Dependent Kinase Inhibitor p16) 0 (DNA, Viral) |
| تواريخ الأحداث: | Date Created: 20200130 Date Completed: 20200917 Latest Revision: 20200917 |
| رمز التحديث: | 20221213 |
| DOI: | 10.1002/path.5387 |
| PMID: | 31994197 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 1096-9896 |
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| DOI: | 10.1002/path.5387 |