title: Epithelial membrane protein 1 negatively regulates cell growth and metastasis in colorectal carcinoma.
abstract: OBJECTIVE
  To determine the expression and function of epithelial membrane protein 1 (EMP1) in colorectal carcinoma.
  
  
  METHODS
  Colorectal samples were taken from cancer lesions and adjacent normal tissue in colorectal cancer patients immediately after endoscopic biopsy. A portion of the sample was either fixed in 4% paraformaldehyde and embedded in paraffin for immunohistochemistry or stored in liquid nitrogen for Western blot. In order to determine protein expression of EMP1 in colorectal cancer (n = 63) and normal tissue (n = 31), semi-quantitative immunohistochemistry and Western blot were utilized. For in vitro studies, the human colorectal cancer cell line SW-480 was maintained in RPMI-1640 medium supplemented with 10% fetal bovine serum. Recombinant lentivirus mediated overexpression of EMP1 in SW-480 cells was quantified by real-time reverse transcription-polymerase chain reaction and Western blot. Control SW-480 cells were transfected with an empty vector. To further study the effect of EMP1 overexpression in SW-480 cells, cell proliferation, apoptosis, migration and invasion assays were conducted.
  
  
  RESULTS
  Expression of EMP1 was significantly lower in colorectal cancer tissue than in normal tissue using both immunohistochemistry (39.7% vs 90.3% of tissues, P < 0.05) and Western blot (0.126 ± 0.022 vs 0.632 ± 0.053, P < 0.05). The level of EMP1 protein expression was not correlated with gender, age, or tumor location. Decreased expression of EMP1 was significantly correlated with T stage, lymph node metastasis, clinic stage, and histological grade in patients with colorectal cancer (P < 0.05). According to Kaplan-Meier analysis, low EMP1 expression correlated significantly with poor overall five-year survival (34.2% vs 64.0% survival, P < 0.05). SW-480 cells transfected with EMP1 had a lower survival fraction, higher cell apoptosis (12.1% ± 1.3% vs 3.1% ± 0.6%, P < 0.05), a significant decrease in migration and invasion (124.0 ± 17.0 and 87.0 ± 12.0, respectively vs 213.0 ± 29.0 and 178.0 ± 21.0, respectively, P < 0.05), higher caspase-9 (0.635 ± 0.063 vs 0.315 ± 0.032, P < 0.05), and lower VEGFC protein expression (0.229 ± 0.021 vs 0.519 ± 0.055, P < 0.05) relative to cells not transfected with EMP1.
  
  
  CONCLUSIONS
  Low EMP1 expression in colorectal cancer is associated with increased disease severity, suggesting that EMP1 may be a negative regulator of colorectal cancer.
authors.affiliation: Guo-Gui Sun, Wan-Ning Hu, Department of Chemoradiotherapy, Tangshan People's Hospital, Tangshan 063000, Hebei Province, China.
authors.forename: Guo-Gui
authors.initials: GG
authors.lastname: Sun
authors.affiliation: Guo-Gui Sun, Wan-Ning Hu, Department of Chemoradiotherapy, Tangshan People's Hospital, Tangshan 063000, Hebei Province, China.
authors.forename: Ya-Di
authors.initials: YD
authors.lastname: Wang
authors.affiliation: Guo-Gui Sun, Wan-Ning Hu, Department of Chemoradiotherapy, Tangshan People's Hospital, Tangshan 063000, Hebei Province, China.
authors.forename: Da-Wei
authors.initials: DW
authors.lastname: Cui
authors.affiliation: Guo-Gui Sun, Wan-Ning Hu, Department of Chemoradiotherapy, Tangshan People's Hospital, Tangshan 063000, Hebei Province, China.
authors.forename: Yun-Jie
authors.initials: YJ
authors.lastname: Cheng
authors.affiliation: Guo-Gui Sun, Wan-Ning Hu, Department of Chemoradiotherapy, Tangshan People's Hospital, Tangshan 063000, Hebei Province, China.
authors.forename: Wan-Ning
authors.initials: WN
authors.lastname: Hu
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001706:Biopsy; D053453:Caspase 9 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D002470:Cell Survival; D015179:Colorectal Neoplasms / Q000378:metabolism*; D004724:Endoscopy; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000378:metabolism*; D011379:Prognosis; D011956:Receptors, Cell Surface / Q000378:metabolism*; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism
chemical_list: D009363:Neoplasm Proteins; D011956:Receptors, Cell Surface; C467486:VEGFC protein, human; D042582:Vascular Endothelial Growth Factor C; C097051:epithelial membrane protein-1; C506433:CASP9 protein, human; D053453:Caspase 9
keywords: Caspase-9; Colorectal carcinoma; Epithelial membrane protein 1; Prognosis; Vascular endothelial growth factor C
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