The role of survivin as a new target of diagnosis and treatment in human cancer.
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.
Yamamoto
T
T
Department of General and Gastroenterological Surgery, Osaka Medical College, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan. sur001@poh.osaka-med.ac.jp
Tanigawa
N
N
D017209:Apoptosis; D002868:Chromosomal Proteins, Non-Histone / Q000032:analysis / Q000037:antagonists & inhibitors / Q000502:physiology*; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D009369:Neoplasms / Q000737:chemistry / Q000175:diagnosis / Q000628:therapy*; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use; D000077022:Survivin
C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D016376:Oligonucleotides, Antisense; D000077022:Survivin