title: Potential significance of EMP3 in patients with upper urinary tract urothelial carcinoma: crosstalk with ErbB2-PI3K-Akt pathway.
abstract: OBJECTIVE
  Upper urinary tract (pyelocalyceal cavities and ureter) urothelial carcinoma is a relatively rare neoplastic disease. Although diagnosis and treatment of this tumor variant have improved significantly, accurate risk stratification remains a challenge. To identify the putative oncogene involved in urothelial carcinoma progression we performed bioinformatics guided experimental investigation targeting chromosome 19q13.
  
  
  METHODS
  We investigated the effects of EMP3 on cancer cell growth, migration and adhesion in transfection and siRNA experiments in vitro. Crosstalk of integrins or ErbB2 with EMP3 was examined by reverse transcriptase-polymerase chain reaction and immunoblot. The potential involvement of epigenetic alterations of EMP3 in vitro and in vivo was analyzed by methylation specific polymerase chain reaction. To validate clinical relevance we measured EMP3 expression at the mRNA and protein levels in a cohort of 77 patients with upper urinary tract urothelial carcinoma and compared prognostic significance in relation to that of ErbB2 expression.
  
  
  RESULTS
  We noted functional crosstalk between ErbB2 and EMP3 in vitro. EMP3 over expression promoted cancer cell proliferation and migration but suppressed cell adhesion in vitro. EMP3 activated the ErbB2-PI3K-AKT pathway to increase cell growth in vitro. In the clinical cohort Kaplan-Meier survival estimates showed that ErbB2 and EMP3 co-expression was the most important indicator of progression-free and metastasis-free survival in patients with upper urinary tract urothelial carcinoma (log rank test p = 0.018 and 0.04, respectively).
  
  
  CONCLUSIONS
  EMP3 is an important prognostic indicator for selecting patients with upper urinary tract urothelial carcinoma for more intensive therapy. EMP3 is an innovative co-targeting candidate for designing ErbB2 based cancer therapy.
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors: Yi-Wen
authors: YW
authors: Wang
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China.
authors: Wei-Ming
authors: WM
authors: Li
authors: Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China; Department of Urology, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China; Department of Urology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan, Republic of China.
authors: Wen-Jeng
authors: WJ
authors: Wu
authors: Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan, Republic of China.
authors: Chee-Yin
authors: CY
authors: Chai
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Department of Microbiology and Immunology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors: Hsiao-Sheng
authors: HS
authors: Liu
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Department of Biochemistry and Molecular Biology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China.
authors: Ming-Derg
authors: MD
authors: Lai
authors: Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China; Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, Republic of China. Electronic address: chownh@mail.ncku.edu.tw.
authors: Nan-Haw
authors: NH
authors: Chow
mesh_terms: D000368:Aged; D002295:Carcinoma, Transitional Cell / Q000209:etiology*; D045744:Cell Line, Tumor; D005260:Female; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology*; D008297:Male; D008562:Membrane Glycoproteins / Q000502:physiology*; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000502:physiology*; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology*; D020239:Receptor Cross-Talk; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000502:physiology*; D015398:Signal Transduction; D014516:Ureteral Neoplasms / Q000209:etiology*
chemical_list: D008562:Membrane Glycoproteins; D051058:Oncogene Protein v-akt; D019869:Phosphatidylinositol 3-Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases; C485157:EMP3 protein, human; C508053:ERBB2 protein, human
keywords: EMP3 protein; carcinoma; human; prognosis; urinary bladder; urothelium