Survivin の甲状腺滤胞上皮细胞増殖および分化に対する.pdf

31 1 16 1 Survivin Role of Survivin on the Proliferation and Differentiation of Thyroid Epithelial Cells Miho Suzuki Department of Endocrinology and Diabetes, Institute of Internal Medicine, Saitama Medical School, Moroyama, Iruma-gun, Saitama 350-0495, Japan Survivin is one of the IAP (inhibitor of apoptosis proteins), which is expressed during embryonic development, but is not expressed in terminal differentiated adult tissue. Overexpression of survivin is observed in a variety of human tumors including thyroid cancers. We examined the role of survivin on the proliferation and differentiation of thyroid epithelial cells. Rat thyroid epithelial cell line FRTL -5 was stably transfected with human sense and antisense survivin genes. FRTL-5 cells transfected with a survivin sense gene (S cells) proliferated without TSH. In the presence of TSH, the proliferation of S cells was significantly faster than that of cells transfected with an empty vector (E cells) or cells transfected with a survivin antisense gene (AS cells). The proliferation of AS cells were retarded as compared with that of E cells. Western blot analysis demonstrated that phosphorylation of Rb protein at serine 795 was enhanced in S cells. Activation of E2F-1 was also enhanced in S cells as demonstrated by gel shift assay. Northern blot analysis showed that expression of Pax -8 mRNA was significantly enhanced in S cells, and was significantly decreased in AS cells. Expression of thyroglobulin (Tg) and TSH receptor (TSHR) mRNA was decreased in AS cells. There was no significant change in TTF-1 and TTF-2 mRNA expression. These observations suggest that survivin enhances the proliferation of thyroid epithelial cells through activation of E2F -1, and also enhance the expression of Pax-8, which then affect t