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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
Author(s) -
Cabrera Ortega Adriana Alicia,
Gonçalves Vinícius de Paiva,
Guimarães Morgana Rodrigues,
Rossa Junior Carlos,
Spolidorio Luis Carlos
Publication year - 2016
Publication title -
journal of oral pathology and medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.887
H-Index - 83
eISSN - 1600-0714
pISSN - 0904-2512
DOI - 10.1111/jop.12413
Subject(s) - 4 nitroquinoline 1 oxide , proliferating cell nuclear antigen , vimentin , immunohistochemistry , epithelial dysplasia , dysplasia , pathology , carcinogenesis , medicine , cancer , cancer research , biology
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, TWIST 1, 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 TWIST 1 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.