Suppression of FHIT Gene on Biological Properties of MEC-1 Cells

Abstract: Objectives: FHIT gene, first isolated by Ohta, et al in 1996, was abnormal in many kinds of tumor cells and was reported as a new cancer suppressor gene. This study was aimed to investigate the status of FHIT gene in mucoepidermoid carcinoma MEC-1 cells and its function in the development of mucoepidermoid carcinoma. Methods: In this study, the status and functions of FHIT gene in MEC cells were observed by RT-PCR, flow cytometery, Western blot, clonal forming assay, tumorigenicity assay, immunohistochemical staining assay, etc. Results: The results showed that there were abnormal transcripts of FHIT gene in MEC cell lines and several squamous carcinoma cell lines. DNA sequencing revealed that the exons 1 to 8 of FHIT gene were not detected in MEC-1 and tongue cancer Tca8113 cells. It can be seen that exogenous Fhit protein could significantly delay the proliferation and reduce cell kinetics of MEC-1 cells in vitro, keep more cells in cell cycle phase S, prolong DT from 24.1 h to 32.4 h. Additionally, we found that exogenous FHIT could remarkably suppress MEC-1 cells of forming tumor loci in murine model by lessen tumor weight, and induce higher differentiation of MEC-1 cells to be mucous cells. Conclusions: Our findings provided the evidences that the FHIT gene is inactivated in MEC-1 cells, and the exogenous FHIT gene could suppress the proliferation, tumorigenicity and could improve the differentiation of MEC-1 cells, in vitro and in vivo.