title: Overexpression of dedicator of cytokinesis I (Dock180) in ovarian cancer correlated with aggressive phenotype and poor patient survival.
abstract: OBJECTIVE
  Dedicator of cytokinesis I (Dock180) is a novel guanine nucleotide exchange factor for Rho guanosine triphosphates (GTPases) important for cell migration. The aim of this study was to evaluate the role of Dock180 in ovarian carcinogenesis.
  
  
  RESULTS
  Using immunohistochemistry, real-time polymerase chain reaction and Western blotting, overexpression of Dock180 RNA and protein was demonstrated in the nucleus and cytoplasm of ovarian cancer cell lines (n = 5) and clinical samples of ovarian borderline tumours (n = 21) and invasive cancers (n = 108) when compared with ovarian epithelial cell lines (n = 3) and benign cystadenomas (n = 10) (P < 0.05). High Dock180 cytoplasmic expression in ovarian cancer (n = 108) was associated significantly with serous histological type, high-grade cancer and advanced stage (P < 0.05), as well as poor overall and disease-free survival (P = 0.004). Using multivariate progression analysis, high Dock180 cytoplasmic expression and advanced cancer stage were found to be independent prognostic factors for short overall survival and disease-free survival (P < 0.05). Exogenous expression of Dock180 by transient transfection enhanced cancer cell migration and invasion, whereas knockdown of Dock180 by an siRNA approach retarded cancer cell migration and invasion in association with down-regulation of matrix metalloproteinase 2.
  
  
  CONCLUSIONS
  Our findings suggest that Dock180 contributes to ovarian carcinogenesis and dissemination and is a potential prognostic marker and therapeutic target.
authors.affiliation: Department of Pathology, The University of Hong Kong, HKSAR, China.
authors.forename: Fung
authors.initials: F
authors.lastname: Zhao
authors.forename: Michelle K Y
authors.initials: MK
authors.lastname: Siu
authors.forename: LiLi
authors.initials: L
authors.lastname: Jiang
authors.forename: Kar Fai
authors.initials: KF
authors.lastname: Tam
authors.forename: Hextan Y S
authors.initials: HY
authors.lastname: Ngan
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Le
authors.forename: Oscar G W
authors.initials: OG
authors.lastname: Wong
authors.forename: Esther S Y
authors.initials: ES
authors.lastname: Wong
authors.forename: Hoi Yan
authors.initials: HY
authors.lastname: Chan
authors.forename: Annie N Y
authors.initials: AN
authors.lastname: Cheung
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis; D015153:Blotting, Western; D002277:Carcinoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D002465:Cell Movement / Q000235:genetics; D003537:Cystadenoma / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D018613:Microscopy, Confocal; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000235:genetics / Q000473:pathology; D010051:Ovarian Neoplasms / Q000201:enzymology* / Q000401:mortality / Q000473:pathology; D010641:Phenotype; D011379:Prognosis; D034741:RNA, Small Interfering; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult; D020744:rac GTP-Binding Proteins / Q000032:analysis / Q000096:biosynthesis*
chemical_list: D014408:Biomarkers, Tumor; C099818:DOCK1 protein, human; D034741:RNA, Small Interfering; D020744:rac GTP-Binding Proteins