title: Expression of Livin in colorectal cancer and its relationship to tumor cell behavior and prognosis.
abstract: BACKGROUND
  Expression of Livin, a member of the inhibitors of apoptosis protein family, is associated with tumor development and progression. The aims of this study were to evaluate whether Livin affects oncogenic biological behavior of colorectal cancer cells, and to document the relationship between its expression and various clinicopathological parameters in colorectal cancer.
  
  
  METHODS
  We investigated the impact of Livin on tumor cell behavior by using the small interfering RNA and pcDNA3.1 vector in SW480 and DKO1 colorectal cancer cell lines. The expression of Livin was investigated by RT-PCR and immunohistochemistry in coloretcal cancer tissues. The apoptotic cells were visualized by TUNEL assay, and proliferative cells were visualized by Ki-67 antibody staining.
  
  
  RESULTS
  Knockdown of Livin suppressed tumor cell migration and invasion in colorectal cancer cells. Knockdown of Livin induced the apoptosis by up-regulating of caspase-3, -7 and PARP activities and the cell cycle arrest by decreasing cyclin D1, cyclin D3, cyclin-dependent kinase 4 and 6, and by inducing p27 expression. The MAPK signaling cascades were significantly blocked by knockdown of Livin. In contrast, overexpression of Livin enhanced tumor cell migration and invasion, and inhibited the apoptosis and cell cycle arrest. The mean apoptotic index (AI) value of Livin positive tumors was significantly lower than AI of Livin negative tumors. However, there was no significant difference between Livin expression and Ki-67 labeling index (KI). Livin expression was significantly increased in colorectal cancer and metastatic lymph node tissues compared to normal colorectal mucosa and non-metastatic lymph node tissues and was associated with tumor stage, lymphovascular invasion, lymph node metastasis and poor survival.
  
  
  CONCLUSIONS
  These results indicate that Livin is associated with tumor progression by increasing tumor cell motility and inhibiting apoptosis in colorectal cancer.
authors.affiliation: Departments of Internal Medicine, Chonnam National University Medical School, Gwangju, Republic of Korea.
authors.forename: Dae-Seong
authors.initials: DS
authors.lastname: Myung
authors.forename: Young-Lan
authors.initials: YL
authors.lastname: Park
authors.forename: Cho-Yun
authors.initials: CY
authors.lastname: Chung
authors.forename: Hyung-Chul
authors.initials: HC
authors.lastname: Park
authors.forename: Jong-Sun
authors.initials: JS
authors.lastname: Kim
authors.forename: Sung-Bum
authors.initials: SB
authors.lastname: Cho
authors.forename: Wan-Sik
authors.initials: WS
authors.lastname: Lee
authors.forename: Kyung-Hwa
authors.initials: KH
authors.lastname: Lee
authors.forename: Jae-Hyuk
authors.initials: JH
authors.lastname: Lee
authors.forename: Young-Eun
authors.initials: YE
authors.lastname: Joo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000368:Aged; D017209:Apoptosis / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics; D059447:Cell Cycle Checkpoints / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D042541:Intracellular Space / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics*; D011379:Prognosis; D015398:Signal Transduction / Q000235:genetics; D016019:Survival Analysis
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C419866:BIRC7 protein, human; D051034:Inhibitor of Apoptosis Proteins; D009363:Neoplasm Proteins
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