title: Role of Raf-kinase inhibitor protein in colorectal cancer and its regulation by hydroxycamptothecine.
abstract: BACKGROUND
  Recently accumulated evidence suggests that Raf kinase inhibitor protein (RKIP) participates in regulation of many signaling pathways and plays an important role in tumorigenesis and tumor metastasis. However, studies investigating the role of RKIP in colorectal cancer have not been reported. The aim of this study was to investigate the role of RKIP on colorectal cancer cell differentiation, progression and its correlation with chemosensitivity.
  
  
  RESULTS
  Immunohistochemical analysis revealed that RKIP expression was higher in non-neoplastic colorectal tissue (NCRCT) and colorectal cancer tissue (CRCT) than that in metastatic lymph node tissue (MLNT) (P <0.05). P-ERK protein expression was higher in MLNT and CRCT than that in NCRCT (P = 0.02). Immunocytochemical analysis further revealed that RKIP expression was higher in the well differentiated cell line SW1116 as compared to that in the poorly differentiated cell line LoVo. Matrigel invasive assay demonstrated that the inhibition of RKIP by short hairpin RNA (shRNA) 271 transfection significantly increased the number of migrated cells (90.67 ± 4.04 vs. 37.33 ± 2.51, P <0.05), whereas over-expression of RKIP by PEBP-1 plasmid transfection significantly suppressed the number of migrated cells (79.24 ± 5.18 vs. 154.33 ± 7.25, P <0.05). Meanwhile, down-regulation of RKIP induced an increase in the cell survival rate by inhibiting apoptosis induced by hydroxycamptothecine.
  
  
  CONCLUSIONS
  RKIP was also found to be associated with cell differentiation, with a higher activity in well differentiated colorectal cancer cells than in poorly differentiated ones. The upregulated expression of RKIP in colorectal cancer cells inhibited cell invasion and metastasis, while downregulation of RKIP reduced chemosensitivity by inhibiting apoptosis induced by HCPT.
authors.affiliation: Department of Intensive Care Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. niefang7@163.com.
authors.forename: Fang
authors.initials: F
authors.lastname: Nie
authors.affiliation: Department of Intensive Care Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. doctorcjg@hotmail.com.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Cao
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China. tongjinlu490@126.com.
authors.forename: Jinlu
authors.initials: J
authors.lastname: Tong
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China. zhumingming@renji.com.
authors.forename: Mingming
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Intensive Care Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China. gaoyuanzhuren@126.com.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Division of Gastroenterology and Hepatology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Digestive Disease, 145 Middle Shandong Road, Shanghai, 200001, China. zhihuaran@vip.163.com.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Ran
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D008198:Lymph Nodes / Q000187:drug effects / Q000473:pathology; D008207:Lymphatic Metastasis; D020935:MAP Kinase Signaling System / Q000235:genetics; D049488:Phosphatidylethanolamine Binding Protein / Q000096:biosynthesis* / Q000235:genetics
chemical_list: C511482:PEBP1 protein, human; D049488:Phosphatidylethanolamine Binding Protein; C527042:hydroxycamptothecinum; D002166:Camptothecin