title: Overexpression of Bcl-2, SOCS 1, 3 and Cdh 1, 2 are associated with the early neoplasic changes in modified 4-nitroquinoline 1-oxide-induced murine oral cancer model.
abstract: BACKGROUND
  The objective was to assess histopathological changes and the expression of proliferating cell nuclear antigen (PCNA), Bcl-2, suppressor of cytokine signaling (SOCS) 1 and 3, Vimentin, TWIST1, and Cdh 1 and 2 in early stages of experimental oral carcinogenesis process using a shorter period of exposure to 4-nitroquinoline oxide (4-NQO) model.
  
  
  METHODS
  In this study, 20 rats were divided into control group (n = 10), sacrificed on the first day of the experiment, and experimental group (n = 10) treated with 50 ppm of 4-NQO solution dissolved in drinking water for 8 and 12 weeks. The histological sections were stained with H&E or subjected to immunohistochemistry for detecting PCNA, Bcl-2, SOCS 1 and 3, and STAT 3. Some specimens were used for verification of Vimentin expression, Cdh 1, Cdh 2, and TWIST1 by RT-qPCR.
  
  
  RESULTS
  At both 8 and 12 weeks, morphological changes occurred mainly in the posterior portion of the tongue and were limited to the epithelial tissue, including moderate to severe dysplasia at 8 weeks, and severe dysplasia with exacerbation of atypical cells at 12 weeks. Expression of SOCS 1 and 3 increased from 8 to 12 weeks (P < 0.05), whereas STAT 3 expression was reduced mainly at 12 weeks (P < 0.05) in comparison with the control group. The expression of all epithelial-mesenchymal transition markers (EMT) was increased after 12 weeks, reaching statistical significance (P < 0.05) for Cdh 1 and 2.
  
  
  CONCLUSIONS
  Together, the results suggested that overexpression of Bcl-2, SOCS 1 and 3, and Cdh 1 and 2 is associated with the early neoplasic changes in modified 4-nitroquinoline 1-oxide-induced murine oral cancer model.
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Univ Estadual Paulista (UNESP), Araraquara, Brazil.
authors.forename: Adriana Alicia
authors.initials: AA
authors.lastname: Cabrera Ortega
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Univ Estadual Paulista (UNESP), Araraquara, Brazil.
authors.forename: Vinícius de Paiva
authors.initials: Vde P
authors.lastname: Gonçalves
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Univ Estadual Paulista (UNESP), Araraquara, Brazil.|Department of Stomatology, School of Dentistry, Universidade de São Paulo (USP), São Paulo, SP, Brazil.
authors.forename: Morgana Rodrigues
authors.initials: MR
authors.lastname: Guimarães
authors.affiliation: Department of Diagnosis and Surgery, School of Dentistry at Araraquara, Univ Estadual Paulista (UNESP), Araraquara, Brazil.
authors.forename: Carlos
authors.initials: C
authors.lastname: Rossa Junior
authors.affiliation: Department of Physiology and Pathology, School of Dentistry at Araraquara, Univ Estadual Paulista (UNESP), Araraquara, Brazil.
authors.forename: Luis Carlos
authors.initials: LC
authors.lastname: Spolidorio
mesh_terms: D015112:4-Nitroquinoline-1-oxide; D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D002273:Carcinogens; D004195:Disease Models, Animal; D058750:Epithelial-Mesenchymal Transition; D008297:Male; D009062:Mouth Neoplasms / Q000139:chemically induced* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D018809:Proliferating Cell Nuclear Antigen / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000096:biosynthesis / Q000235:genetics; D000071223:Suppressor of Cytokine Signaling 3 Protein / Q000096:biosynthesis / Q000235:genetics; D051879:Twist-Related Protein 1 / Q000096:biosynthesis / Q000235:genetics; D014746:Vimentin / Q000096:biosynthesis / Q000235:genetics
chemical_list: C000617196:Bcl2 protein, rat; D014408:Biomarkers, Tumor; C000610228:CDH1 protein, rat; D015820:Cadherins; D002273:Carcinogens; C570099:N-cadherin, rat; D009419:Nerve Tissue Proteins; D018809:Proliferating Cell Nuclear Antigen; D019253:Proto-Oncogene Proteins c-bcl-2; C491589:Socs1 protein, rat; C491410:Socs3 protein, rat; D000071222:Suppressor of Cytokine Signaling 1 Protein; D000071223:Suppressor of Cytokine Signaling 3 Protein; D051879:Twist-Related Protein 1; C497754:Twist1 protein, rat; D014746:Vimentin; D015112:4-Nitroquinoline-1-oxide
keywords: 4-nitroquinoline-1-oxide; cadherins; oral cancer; proliferating cell nuclear antigen; rat