TFAP2E acts as a tumor suppressor by regulating cell cycle progression in oral squamous cell carcinoma cells

Abstract

TFAP2E, a member of the activator protein-2 transcription factor family, is considered to act as a tumor suppressor. Lower TFAP2E expression is associated with poor prognosis in patients with different cancer types. TFAP2E gene is located on chromosome 1q34, where is commonly deleted region in the cancer genome. Our previous research indicated that TFAP2E suppresses cell growth by regulating cell cycle progression from the G2 to M phase. However, as the analyses were performed using asynchronized cells, other possibilities cannot be ruled out. The present study aimed to analyze the effects of TFAP2E silencing on synchronized cells. Human oral squamous cell carcinoma (OSCC)-derived Ca9–22 cells were stably transfected with TFAP2E-short hairpin RNA and synchronized to the late-G1 phase using double thymidine block. Cell cycle progression rate was analyzed by periodically examining cell cycle distribution patterns using fluorescence-activated cell sorting analysis. TFAP2E-knockdown cells showed a rapid exit from the M-phase compared with control cells; meanwhile, no difference was observed between the cells until the end of S-phase. Additionally, rapid M-phase exit was not observed in TFAP2E-knockdown cells following release from nocodazole-mediated synchronization to the G2/M-phase. These observations indicated that TFAP2E-knockdown results in rapid cell cycle progression from the G2 to M phase. Overall, current findings suggest that TFAP2E acts as a tumor suppressor by regulating cell cycle progression at least in OSCC cells.