title: The role of KIF14 in patient-derived primary cultures of high-grade serous ovarian cancer cells.
abstract: OBJECTIVE
  Previously, it has been shown that KIF14 mRNA is overexpressed in ovarian cancer (OvCa), regardless of histological subtype. KIF14 levels are independently predictive of poor outcome and increased rates of recurrence in serous OvCa patients. Furthermore, it has been shown that KIF14 also controls the in vivo tumorigenicity of OvCa cell lines. In this study, we evaluate the potential of KIF14 as a therapeutic target through selective inhibition of KIF14 in primary high-grade serous patient-derived OvCa cells.
  
  
  METHODS
  To assess the dependence of primary serous OvCa cultures on KIF14, protein levels in 11 prospective high grade serous ovarian cancer samples were increased (KIF14 overexpression by transfection) or decreased (anti-KIF14 shRNA) in vitro, and proliferative capacity, anchorage independence and xenograft growth were assessed.
  
  
  RESULTS
  Seven of eleven samples demonstrated increased/decreased in vitro proliferation in response to KIF14 overexpression/knockdown, respectively. When examining in vitro tumorigenicity (colony formation) and in vivo growth (subcutaneous xenografts) in response to KIF14 manipulation, none of the samples demonstrated growth in soft agar (11 samples), or xenograft growth (4 samples).
  
  
  CONCLUSIONS
  Although primary high-grade serous OvCa cells may depend on KIF14 for in vitro proliferation we were unable to demonstrate a role for KIF14 on tumorigenicity or develop an in vivo model for assessment. We have, however developed an effective in vitro method to evaluate the effect of target gene manipulation on the proliferative capacity of primary OvCa cultures.
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. brigitte.theriault@uhnresearch.ca.
authors.forename: Brigitte L
authors.initials: BL
authors.lastname: Thériault
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. Paulina.Cybulska@mail.utoronto.ca.|Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada. Paulina.Cybulska@mail.utoronto.ca.|Division of Gynecological Oncology, University Health Network, Toronto, ON, Canada. Paulina.Cybulska@mail.utoronto.ca.
authors.forename: Paulina
authors.initials: P
authors.lastname: Cybulska
authors.affiliation: Department of Pathology, University Health Network, Toronto, ON, Canada. patricia.shaw@uhn.ca.|Princess Margaret Hospital, University Health Network Tissue Bank, Toronto, ON, Canada. patricia.shaw@uhn.ca.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Shaw
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. brenda@gallie.ca.|Division of Visual Science, Toronto Western Hospital Research Institute, Toronto, ON, Canada. brenda@gallie.ca.|Departments of Medical Biophysics, Molecular Genetics, and Ophthalmology, University of Toronto, Toronto, ON, Canada. brenda@gallie.ca.
authors.forename: Brenda L
authors.initials: BL
authors.lastname: Gallie
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, University Health Network, Toronto, ON, Canada. marcus.bernardini@uhn.ca.|Department of Obstetrics and Gynecology, University of Toronto, Toronto, ON, Canada. marcus.bernardini@uhn.ca.|Division of Gynecological Oncology, University Health Network, Toronto, ON, Canada. marcus.bernardini@uhn.ca.|Princess Margaret Cancer Centre, Rm M700, 610 University Ave, Toronto, Ontario, M5G 2M9, Canada. marcus.bernardini@uhn.ca.
authors.forename: Marcus Q
authors.initials: MQ
authors.lastname: Bernardini
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D005260:Female; D015870:Gene Expression; D006801:Humans; D016547:Kinesins / Q000502:physiology*; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D018297:Neoplasms, Cystic, Mucinous, and Serous / Q000378:metabolism* / Q000473:pathology; D015513:Oncogene Proteins / Q000502:physiology*; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000473:pathology; D061251:Primary Cell Culture
chemical_list: D015513:Oncogene Proteins; C502598:KIF14 protein, human; D016547:Kinesins