title: Upregulation of RASGRP3 expression in prostate cancer correlates with aggressive capabilities and predicts biochemical recurrence after radical prostatectomy.
abstract: BACKGROUND
  This study was undertaken to investigate the expression of guanyl nucleotide-releasing protein for Ras 3 (RasGRP3) in the cell lines and tissues in BPH and prostate cancer (PCa), as well as its associations with cancer invasion and prognosis in prostate carcinomas.
  
  
  METHODS
  Expression analysis of RasGRP3 was accomplished using immunohistochemical staining of PCa and BPH tissues. Pearson's χ2 test was used to analyze the association between RasGRP3 expression and specific clinical parameters. Survival and PSA relapse curves were evaluated using the Kaplan-Meier curves and log-rank tests, and the differences were assessed using the Cox regression methods. In addition, human PCa cell lines PC-3, DU145, LNCaP, PC3M-1E8, PC3M-2B4 and BPH-1 were examined for expression of RasGRP3 using western blot and quantitative polymerase chain reaction (Q-PCR) analysis. After PC-3 cells were transfected by small interfering RNA targeting RasGRP3, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and migratory assays were employed to determine the vitality and aggressive capability of tumor cell in vitro.
  
  
  RESULTS
  Expression of RasGRP3 was significantly correlated (P=0.038 and P=0.021) with Gleason score (< or =6 versus > or =7) and T stage (T1-T2 versus T3-T4), respectively. PCa with RasGRP3-positive expression may increase the risk of PSA recurrence and decrease cancer-specific survival (P=0.0291 and P=0.0044). The expression of RasGRP3 was also associated with PSA recurrence and cancer-specific survival in univariate (P<0.001 and P<0.001) and multivariate analyses (P<0.001 and P=0.003). RasGRP3 mRNA and proteins were found to be positively expressed in PCa cell lines. There was higher expression of RasGRP3 in PC-3, DU145 and PC3M-1E8 than in LNCaP, PC3M-2B4 and BPH-1. Knockdown of RasGRP3 inhibited the proliferation, migration and invasion capabilities of PC-3 cells.
  
  
  CONCLUSIONS
  These data suggested that elevated RasGRP3 expression may play a key role in the malignant progression of PCa, especially in invasion and metastasis, and may be a potential marker of biochemical recurrence.
authors.affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: X
authors.initials: X
authors.lastname: Zeng
authors.affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Dermatology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: J
authors.initials: J
authors.lastname: Tao
authors.affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: T
authors.initials: T
authors.lastname: Lu
authors.affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: C
authors.initials: C
authors.lastname: Yang
authors.affiliation: Department of Urology, Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: B
authors.initials: B
authors.lastname: Lee
authors.affiliation: Department of Urology, Tonji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People's Republic of China.
authors.forename: Z
authors.initials: Z
authors.lastname: Ye
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation / Q000502:physiology; D055785:Gene Knockdown Techniques; D020662:Guanine Nucleotide Exchange Factors / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D007610:Kallikreins / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D011379:Prognosis; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011468:Prostatectomy / Q000379:methods; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000235:genetics; D034741:RNA, Small Interfering / Q000008:administration & dosage / Q000235:genetics; D015854:Up-Regulation; D020663:ras Guanine Nucleotide Exchange Factors
chemical_list: D020662:Guanine Nucleotide Exchange Factors; C413212:RASGRP3 protein, human; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D020663:ras Guanine Nucleotide Exchange Factors; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen