Yamamoto T, Tanigawa N
Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan.
Med Electron Microsc. 2001 Dec;34(4):207-12. doi: 10.1007/s007950100017.
Survivin has recently been identified as a novel inhibitor of apoptosis (IAP). Unlike other members of the IAP family, survivin is characterized by a unique structure that contains a single baculovirus IAP repeat and no really interesting new gene (RING) finger motifs, and it is expressed in many common human cancers, but not in normal tissues. Survivin regulates the G(2)/M phase of the cell cycle by associating with mitotic spindle microtubules, and it directly inhibits caspase-3 and caspase-7 activity. During tumorigenesis, survivin expression is inversely correlated with apoptosis inhibition and positively correlated with proliferation and angiogenesis. Inhibition of apoptosis by survivin predicts poor prognosis and shorter survival in human cancers. The molecular detection of occult cancer by the targeting of survivin as a novel molecular marker is useful, and micrometastasis detected by immunohistochemical staining for survivin reveals inhibition of apoptosis and the acceleration of cell proliferation. In in-vitro and in-vivo studies, survivin targeting with antisense and survivin mutants induces apoptosis, reduces tumor growth potential, and sensitizes cells to chemotherapeutic drugs and X-irradiation. These results suggest that survivin may have the potential to function as a new target for the diagnosis and treatment of cancer.
生存素最近被确定为一种新型凋亡抑制因子（IAP）。与IAP家族的其他成员不同，生存素具有独特的结构，其包含单个杆状病毒IAP重复序列且无真正有趣的新基因（RING）指基序，并且它在许多常见人类癌症中表达，但在正常组织中不表达。生存素通过与有丝分裂纺锤体微管结合来调节细胞周期的G(2)/M期，并且它直接抑制半胱天冬酶-3和半胱天冬酶-7的活性。在肿瘤发生过程中，生存素的表达与凋亡抑制呈负相关，与增殖和血管生成呈正相关。生存素对凋亡的抑制预示着人类癌症的预后不良和生存期缩短。以生存素作为新型分子标志物靶向检测隐匿性癌症的分子检测方法很有用，通过免疫组织化学染色检测生存素发现的微转移揭示了凋亡抑制和细胞增殖加速。在体外和体内研究中，用反义核酸和生存素突变体靶向生存素可诱导凋亡、降低肿瘤生长潜能，并使细胞对化疗药物和X射线辐射敏感。这些结果表明，生存素可能有潜力作为癌症诊断和治疗的新靶点。
