Overexpression of tuberous sclerosis complex 2 exerts antitumor effect on oral cancer cells

Abstract

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Tuberous sclerosis is caused by mutations in tuberous sclerosis complex (TSC) 2 on chromosome 16p13.3, encoding tuberin which is thought to be essential for p27Kip1 to regulate the cell cycle. In this study, we conducted to examine whether overexpression of TSC2 can affect the growth of oral cancer cells which have different expression level of p27Kip1 protein and also investigated whether tuberin expression can be an useful prognostic factor in oral cancer patients. We constructed an expression vector containing sense-oriented rat TSC2 cDNA with pcDNA3.1. We transfected oral cancer cells, B88t (high expression of p27Kip1 protein) and HI (low expression of p27Kip1 protein) with the sense expression vector to up-regulate the expression of TSC2 gene. Moreover, tuberin and p27Kip1 expression was investigated by immunohistochemistry in tissue samples from 100 patients with oral cancer. Associations of tuberin expression with clinicopathological characteristics and patient survival were also analyzed. Overexpression of TSC2 exerted the growth inhibitory effect of B88t and HI in vitro and also exerted the antitumor effect on oral cancer cells whether they have high expression of p27Kip1 protein or not in vivo. In addition, there was significant association found between tuberin expression and therapeutic effect (p<0.01), patient outcome (p<0.01), the 5-year-survival rates(p<0.01). In general, loss of p27Kip1 thought to be associated with disease progression and an unfavorable outcome in several malignancies including an oral cancer. But, these findings suggest that overexpression of TSC2 may exert the antitumor effect on oral cancer cells whether they have high expression of p27Kip1 protein or not, and expression of tuberin may play an important role in the progression of oral cancer and is considered to be a useful prognostic factor in oral cancer patients.