title: Impact of the adaptor protein GIPC1/Synectin on radioresistance and survival after irradiation of prostate cancer.
abstract: OBJECTIVE
  Studies have shown that GIPC1/Synectin is an essential adaptor protein of receptors that play an important role in cancer progression and therapy resistance. This is the first study to explore the role of GIPC1/Synectin in radioresistance of prostate cancer and as a possible predictive marker for outcome of primary radiation therapy.
  
  
  METHODS
  The effect of RNA interference-mediated GIPC1/Synectin depletion on clonogenic cell survival after irradiation with 0, 2, 4, or 6 Gy was assayed in two different GIPC1/Synectin-expressing human prostate cancer cell lines. The clinical outcome data of 358 men who underwent radiotherapy of prostate cancer with a curative intention were analyzed retrospectively. Uni- and multivariate analysis was performed of prostate-specific antigen recurrence-free survival and overall survival in correlation with protein expression in pretreatment biopsy specimens. Protein expression was evaluated by standard immunohistochemistry methods.
  
  
  RESULTS
  In cell culture experiments, no change was detected in radiosensitivity after depletion of GIPC1/Synectin in GIPC1/Synectin-expressing prostate cancer cell lines. Furthermore, there was no correlation between GIPC1/Synectin expression in human pretreatment biopsy samples and overall or biochemical recurrence-free survival after radiotherapy in a retrospective analysis of the study cohort.
  
  
  CONCLUSIONS
  Our results do not show a predictive or prognostic function of GIPC1/Synectin expression for the outcome of radiotherapy in prostate cancer. Furthermore, our in vitro results do not support a role of GIPC1 in the cellular radiation response. However, the role of GIPC1 in the progression of prostate cancer and its precursors should be subject to further research.
authors.affiliation: Department of Radiation Oncology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Singer
authors.forename: Y
authors.initials: Y
authors.lastname: Deuse
authors.forename: U
authors.initials: U
authors.lastname: Koch
authors.forename: T
authors.initials: T
authors.lastname: Hölscher
authors.forename: D
authors.initials: D
authors.lastname: Pfitzmann
authors.forename: C
authors.initials: C
authors.lastname: Jakob
authors.forename: S
authors.initials: S
authors.lastname: Hehlgans
authors.forename: G B
authors.initials: GB
authors.lastname: Baretton
authors.forename: A
authors.initials: A
authors.lastname: Rentsch
authors.forename: M
authors.initials: M
authors.lastname: Baumann
authors.forename: M H
authors.initials: MH
authors.lastname: Muders
authors.forename: M
authors.initials: M
authors.lastname: Krause
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002470:Cell Survival; D015331:Cohort Studies; D018572:Disease-Free Survival; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology / Q000532:radiotherapy*; D034622:RNA Interference; D011836:Radiation Tolerance / Q000235:genetics*; D015996:Survival Rate; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D014410:Tumor Stem Cell Assay
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C492009:GIPC1 protein, human