Differential Expression of c-fos Proto-Oncogene in Normal Oral Mucosa versus Squamous Cell Carcinoma

Abstract

Background: The c-Fos nuclear protein dimerizes with Jun family proteins to form the transcription factor AP-1<br />complex which participates in signal transduction and regulation of normal cellular processes. In tumorigenesis, c-Fos<br />promotes invasive growth through down-regulation of tumor suppressor genes but its role in oral carcinogenesis is not<br />clear. Objectives: This study concerned c-fos gene expression in normal and malignant tissues of the oral cavity, with<br />attention to associations between expression status and clinico-pathological profiles of OSCC patients. Method: A total<br />of 65 histopathologically confirmed OSCC tissue samples were included in case group along with an equal number of<br />age and sex-matched normal tissue samples of oral cavity for the control group. c-Fos protein and m-RNA expressions<br />were analyzed using immunohistochemistry and qRT-PCR, respectively. Results: A significant low expression of c-Fos<br />protein was observed in OSCC cases than normal control subjects (p= <0.001). The mean percent positivity of c-Fos<br />protein in cases vs. controls was 24.91± 2.7 vs. 49.68± 2.2 (p= <0.001). Most OSCC tissue samples showed weak or<br />moderate c-Fos expression whereas 53.8% of normal tissue sections presented with strong immunostaining. Moreover,<br />the relative m-RNA expression for the c-fos gene was significantly decreased in case group (0.93± 0.48) as compared to<br />the control group (1.22± 0.87). Majority of c-Fos positive cases were diagnosed with well developed tumor. The mean<br />percent positivity of c-Fos protein was significantly lower in higher grade tumor as compared with normal oral mucosa<br />(p= < 0.001). Conclusion: The present study suggested that the c-fos gene is downregulated in oral carcinomas. The<br />disparity of c-Fos protein levels in different pathological grades of tumor and normal oral tissue samples may indicate<br />that loss of c-Fos expression is related with the progression of OSCC.