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Biotech Histochem. 2016;91(4):263-8. doi: 10.3109/10520295.2016.1144078. Epub 2016 Mar 16.

Expression of ATP6V1C1 during oral carcinogenesis.

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a Department of Biosciences and Oral Diagnosis , Institute of Science and Technology, UNESP - Univ Estadual Paulista, São José dos Campos , São Paulo , Brazil.
b University Braz Cubas , Mogi das Cruzes, São Paulo , Brazil.
c Human Anatomy and Embryology Area, Department of Functional Biology and Health Sciences , University of Vigo , Pontevedra , Spain.
d Oral Medicine, Oral Surgery and Implantology Unit, Faculty of Medicine and Dentistry , Santiago de Compostela , Spain.
e Department of Pathology and Forensic Sciences , University Hospital and School of Medicine of Santiago de Compostela , Santiago de Compostela , Spain.
f Smoking Cessation Program, Area of Cardiology, Heart Institute, University of São Paulo School of Medicine, Hospital das Clínicas , São Paulo , Brazil.


We investigated the gene and protein expressions of V-type ATPase protein subunit C1 (ATP6V1C1) in cases of oral squamous cell carcinoma (OSCC) and contralateral normal mucosa in smokers, nonsmokers and former smokers. Subjects were separated into five groups of 15: group 1, smokers with OSCC; group 2, normal contralateral mucosa of OSCC patients; group 3, chronic smokers; group 4, former smokers who had stopped smoking 1 year earlier; group 5, individuals who had never smoked. Exfoliative cytology specimens from oral mucosa of smokers, former smokers and nonsmokers showed normal gene and protein expression. We found significantly greater gene expression in the OSCC group than in the nonsmoker groups. No difference in gene expression was observed between normal contralateral mucosa and nonsmoker groups, smoker and nonsmoker groups or former smoker and nonsmoker groups. We observed intense immunostaining for ATP6V1C1 protein in all cases of OSCC and weak or no staining in smoker, former smoker and nonsmoker groups. Significantly greater expression of ATP6V1C1 protein was observed in the OSCC group compared to the other groups, which supports the role of ATP6V1C1 in effecting changes associated with oral cancer. Analysis of the mucosae of chronic smokers, former smokers and the normal contralateral mucosa of patients with OSCC showed unaltered ATP6V1C1 gene and protein expression. Early stages of carcinogenesis, represented by altered epithelium of chronic smokers, had neither gene nor protein alterations as seen in OSCC. Therefore, we infer that the changes in ATP6V1C1 occur during later stages of carcinogenesis. Our preliminary study provides a basis for future studies of using ATP6V1C1 levels for detecting early stage OSCC.


ATP6V1C1; gene expression; immunocytochemistry; oral cancer; polymerase chain reaction; smoking; squamous cell carcinoma

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