title: Oncogenic potential of cyclin kinase subunit-2 in cholangiocarcinoma.
abstract: BACKGROUND
  Cyclin kinase subunit-2 (Cks2), a member of the human Cks family, plays an important role in the regulation of meiosis and mitosis; and its abnormal expression is usually associated with carcinogenesis. However, its exact functions and molecular mechanisms remain unclear.
  
  
  OBJECTIVE
  To observe Cks2 expression in cholangiocarcinoma and explore its role in the carcinogenesis of cholangiocarcinoma and possible mechanism.
  
  
  METHODS
  Cks2 expression in cholangiocarcinoma was detected with immunostaining and RT-PCR. MTT, colony formation, immunofluorescence, flow cytometry and Western blotting were performed to explore the role of Cks2 in cholangiocarcinoma and possible mechanism.
  
  
  RESULTS
  Cks2 was significantly elevated in cholangiocarcinoma tissues and its over-expression was associated with poor differentiation, CA19-9 and poor prognosis. Furthermore, Cks2 down-regulation inhibited cholangiocarcinoma cell proliferation and colony formation in vitro, and the growth of cholangiocarcinoma xenografts in animals; especially, enhanced the sensitivity of cholangiocarcinoma cells to chemotherapy. We further found that Cks2 knockdown induced cholangiocarcinoma cell cycle arrest in G2/M phase through down-regulation of Cyclin A and Cyclin B1 and Bax up-regulation and activation, mitochondrial membrane permeabilization and caspase-3 activation, which resulted in facilitating cholangiocarcinoma apoptosis.
  
  
  CONCLUSIONS
  These findings suggest that Cks2 may serve as an independent prognostic factor in patients with cholangiocarcinoma, and play an important role in the carcinogenesis of cholangiocarcinoma by facilitating cell cycle progression and Bax-mediated mitochondrial caspase-dependent apoptosis.
authors.affiliation: Center for Laboratory, The First Affiliated Hospital of Xiamen University, Xiamen, China.
authors.forename: Dong-Yan
authors.initials: DY
authors.lastname: Shen
authors.forename: Yi-Hong
authors.initials: YH
authors.lastname: Zhan
authors.forename: Qian-Ming
authors.initials: QM
authors.lastname: Wang
authors.forename: Gang
authors.initials: G
authors.lastname: Rui
authors.forename: Zhi-Ming
authors.initials: ZM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001650:Bile Duct Neoplasms / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D001653:Bile Ducts, Intrahepatic / Q000201:enzymology* / Q000473:pathology; D015153:Blotting, Western; D018395:CA-19-9 Antigen / Q000097:blood; D042846:CDC2-CDC28 Kinases / Q000235:genetics / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D018281:Cholangiocarcinoma / Q000097:blood / Q000201:enzymology* / Q000235:genetics / Q000401:mortality / Q000473:pathology / Q000601:surgery; D019925:Cyclin A / Q000378:metabolism; D056744:Cyclin B1 / Q000378:metabolism; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D059565:G2 Phase Cell Cycle Checkpoints; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors; D014162:Transfection; D047368:Tumor Burden; D015854:Up-Regulation; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; D018395:CA-19-9 Antigen; C534699:CCNB1 protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D019925:Cyclin A; D056744:Cyclin B1; D012333:RNA, Messenger; D051028:bcl-2-Associated X Protein; D042846:CDC2-CDC28 Kinases; C083689:CKS2 protein, human; C505407:CASP3 protein, human; D053148:Caspase 3