Zhou Shanghui, Li Lili, Jian Xinchun, Ou Xinrong, Jiang Haiying, Yao Zhigang, Xu Chunjiao, Peng Jieying
Department of Oral and Maxillofacial Surgery, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China.
Oncol Rep. 2008 Nov;20(5):1085-91.
Survivin is a crucial node molecule involved in apoptosis, cell division and drug discovery. Up-regulation of survivin in the tissues of oral submucous fibrosis (OSF) and oral squamous cell carcinoma (OSCC) originated from OSF has already been demonstrated. Survivin Thr34 phosphorylation is involved in the inhibition of apoptosis and cell division. To determine the potential involvement of survivin Thr34 phosphorylation in carcinogenesis of OSF, 40 OSFs, 42 OSCCs originated from OSF and 10 normal tissues from surgical specimens were studied. Immunohistochemistry showed that the positive staining rate of the survivin phosphorylation on Thr34 in OSCC originated from OSF group was significantly higher than that in OSF group (P<0.01), and none in the normal oral mucosa specimens. Survivin phosphorylation on Thr34 is predominantly located in the nucleus, which account for its function in apoptosis at cell division. Western blotting analysis showed increasing expression of survivin Thr34 phosphorylation, cyclin B1 and p34cdc2 in carcinogenesis of OSF. Furthermore, p34cdc2-cyclin B1 kinase was confirmed to phosphorylate survivin on Thr34 in carcinogenesis of OSF by immunoprecipitation and immunoblot. These results suggest that the phosphorylation of survivin on Thr34 critically regulate survivin and plays an important role during the malignant transformation of OSF, which will provide an indication to early diagnosis and therapy in carcinogenesis of OSF.
生存素是参与细胞凋亡、细胞分裂和药物研发的关键节点分子。口腔黏膜下纤维化（OSF）组织及源自OSF的口腔鳞状细胞癌（OSCC）组织中生存素的上调已得到证实。生存素Thr34磷酸化参与细胞凋亡和细胞分裂的抑制过程。为确定生存素Thr34磷酸化在OSF癌变中的潜在作用，对40例OSF、42例源自OSF的OSCC以及10例手术标本中的正常组织进行了研究。免疫组织化学显示，源自OSF的OSCC组中生存素Thr34磷酸化的阳性染色率显著高于OSF组（P<0.01），而正常口腔黏膜标本中均无阳性染色。生存素Thr34磷酸化主要位于细胞核中，这与其在细胞分裂时的凋亡功能相关。蛋白质印迹分析表明，在OSF癌变过程中，生存素Thr34磷酸化、细胞周期蛋白B1和p34cdc2的表达增加。此外，通过免疫沉淀和免疫印迹证实，在OSF癌变过程中p34cdc2 - 细胞周期蛋白B1激酶可使生存素Thr34磷酸化。这些结果表明，生存素Thr34磷酸化对生存素起着关键调节作用，并在OSF的恶性转化过程中发挥重要作用，这将为OSF癌变的早期诊断和治疗提供线索。
