title: High expression of wee1 is associated with malignancy in vulvar squamous cell carcinoma patients.
abstract: BACKGROUND
  Vulvar squamous cell carcinoma is a cancer form with increasing incidence rate and few treatment options. Wee1 is a central regulator of the G2/M DNA-damage checkpoint, and has in previous studies been described as a prognostic biomarker and a potential target for therapy in other cancer forms.
  
  
  METHODS
  In the present study we analyzed the expression of Wee1 in a panel of 297 vulvar tumors by immunohistochemistry. Furthermore, siRNA transfections were carried out in two vulvar cancer cell lines (SW-954 and CAL-39) in order to study the effect on cell cycle distribution (flow cytometry) and proteins (western blot) involved in DNA damage response and apoptosis.
  
  
  RESULTS
  Wee1 kinase is increased in vulvar squamous cell carcinomas, as compared to expression in normal epithelium, and a high Wee1 expression is associated with markers of malignancy, such as lymph node metastasis and poor differentiation. Our in vitro results showed that siRNA mediated Wee1 silencing only led to a modest reduction in viability, when examined in vulvar cancer cell lines. Nonetheless, a marked increase in DNA damages, as assessed by augmented levels of γ-H2AX, was observed in both cell lines in the absence of Wee1.
  
  
  CONCLUSIONS
  Our results suggest that Wee1 may be involved in the progression of vulvar carcinomas. Based on our in vitro results, Wee1 is unlikely to function as a target for mono-treatment of these patients.
authors.affiliation: Department of Pathology, The Norwegian Radium Hospital, Oslo University Hospital and University of Oslo, Oslo, Montebello 0310, Norway.
authors.forename: Gry Irene
authors.initials: GI
authors.lastname: Magnussen
authors.forename: Ellen
authors.initials: E
authors.lastname: Hellesylt
authors.forename: Jahn M
authors.initials: JM
authors.lastname: Nesland
authors.forename: Claes G
authors.initials: CG
authors.lastname: Trope
authors.forename: Vivi Ann
authors.initials: VA
authors.lastname: Flørenes
authors.forename: Ruth
authors.initials: R
authors.lastname: Holm
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins / Q000032:analysis / Q000096:biosynthesis*; D018450:Disease Progression; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009687:Nuclear Proteins / Q000032:analysis / Q000096:biosynthesis*; D011379:Prognosis; D011505:Protein-Tyrosine Kinases / Q000032:analysis / Q000096:biosynthesis*; D034741:RNA, Small Interfering; D014162:Transfection; D014846:Vulvar Neoplasms / Q000378:metabolism* / Q000473:pathology
chemical_list: D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D034741:RNA, Small Interfering; D011505:Protein-Tyrosine Kinases; C499349:WEE1 protein, human