title: [Regulation mechanism study of S100A6 on invasion and metastasis in gastric cancer].
abstract: OBJECTIVE
  To detect the expression of S100A6 in gastric cancer, and to investigate the regulation mechanism of S100A6 in invasion and metastasis of gastric cancer.
  
  
  METHODS
  Expression of S100A6 protein in gastric cancer specimens, tissue adjacent to cancer, liver and lymph node metastasis tissue specimens was detected by immunohistochemical staining in 166 patients with gastric cancer from January 1995 to December 2001. Their association with clinicopathological factors was analyzed. Chromatin Immunoprecipitation-chip was used to detect the downstream factors potentially regulated by S100A6 in gastric cancer cell lines KATO3. S100A6 gene was transfected into gastric cancer cell line AGS, and cell invasion experiment and real time Q-polymerase chain reaction(RT Q-PCR) were used to detect the cell invasive ability and the mRNA expression of invasion-related factors (CDK5 and FLJ12438) in transfection group, negative control group and blank control group, respectively.
  
  
  RESULTS
  Low expression of S100A6 protein was found in cytoplasm of peritumoral tissues. In gastric cancer, liver and lymph node metastasis tissues, S100A6 protein expression was up-regulated in cytoplasm and (or) nuclei, especially in the tumor cells of invasive edge. The expression rates of gastric cancer, liver and lymph node metastasis tissues were 67.5%(112/166), 92.9%(26/28) and 100% (30/30) respectively. The high expression of S100A6 was associated with tumor local invasion, lymph node metastasis, cancer embolus, distant metastasis and TNM stages(all P<0.05). The transmembrane cell number was 31.3±5.5 in the S100A6 transfection group, significantly higher than that in negative control group (7.7±1.5) and blank control group (9.3±2.1)(both P<0.05), indicating an increase of cell invasion after S100A6 transfection. In transfection group, CDK5 mRNA expression was significantly higher than that in negative control group and blank control group(P<0.05). While FLJ1243 mRNA expression was similar among the three groups(P<0.05).
  
  
  CONCLUSIONS
  S100A6 may affect the malignant biological behavior of gastric cancer cells by regulating the expressions of down-stream invasion-associated factors, such as CDK5.
authors.affiliation: Department of Gastrointestinal Cancer Surgery, Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education), Peking University Cancer Hospital and Institute, Beijing 100142, China. jiafuj@gmail.com.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Xiao-hong
authors.initials: XH
authors.lastname: Wang
authors.forename: Zi-yu
authors.initials: ZY
authors.lastname: Li
authors.forename: Zhao-de
authors.initials: ZD
authors.lastname: Bu
authors.forename: Ai-wen
authors.initials: AW
authors.lastname: Wu
authors.forename: Lian-hai
authors.initials: LH
authors.lastname: Zhang
authors.forename: Xiao-jiang
authors.initials: XJ
authors.lastname: Wu
authors.forename: Xiang-long
authors.initials: XL
authors.lastname: Zong
authors.forename: Jia-fu
authors.initials: JF
authors.lastname: Ji
mesh_terms: D018797:Cell Cycle Proteins / Q000378:metabolism*; D006801:Humans; D008207:Lymphatic Metastasis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000378:metabolism* / Q000473:pathology; D014162:Transfection; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D000075383:S100 Calcium Binding Protein A6; D009418:S100 Proteins; C055351:S100A6 protein, human