title: Clinicopathological significance of expression of p-c-Jun, TCF4 and beta-Catenin in colorectal tumors.
abstract: BACKGROUND
  A recent study has shown that phosphorylated c-Jun (p-c-Jun) interacts with TCF4 to form a complex that cooperatively enhances their transcriptional activity in the presence of beta-Catenin, and that their interaction is critical for mouse intestinal tumorigenesis. To determine the significance of these three proteins in human colorectal tumors, we analyzed their nuclear expression by immunohistochemistry.
  
  
  METHODS
  we analyzed their nuclear expression by immunohistochemistry using paraffin-embedded specimens of 68 resected colorectal tumors, which consisted of 19 adenomas, 14 high-grade intraepithelial neoplasia (HGINs) and 35 adenocarcinomas. We also analyzed the expression of MMP7, which has functional AP-1 and TCF binding sites in its promoter.
  
  
  RESULTS
  Expression of p-c-Jun, TCF4 and beta-Catenin were significantly higher in adenomas than in the adjacent normal epithelia. Expression of p-c-Jun and beta-Catenin in HGINs and adenocarcinomas were also significantly higher than in the adjacent normal epithelia. p-c-Jun expression, but not TCF4 and beta-Catenin, was higher in adenomas and HGINs than in adenocarcinomas, in which p-c-Jun expression was negatively correlated with pT stage progression. Furthermore, significant correlations of expression were observed between p-c-Jun and TCF4 (r = 0.25, p = 0.04), TCF4 and beta-Catenin (r = 0.30, p = 0.01), p-c-Jun and MMP7 (r = 0.26, p = 0.03), and TCF4 and MMP7 (r = 0.39, p = 0.0008), respectively.
  
  
  CONCLUSIONS
  These results suggest that nuclear expression of p-c-Jun, TCF4 and beta-Catenin have important roles in human colorectal tumor development and that p-c-Jun may play a pivotal role in the earlier stages of tumor development.
authors.affiliation: Department of Medical Oncology, Hokkaido University Graduate School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan. kayoko-t@med.hokudai.ac.jp
authors.forename: Kayoko
authors.initials: K
authors.lastname: Takeda
authors.forename: Ichiro
authors.initials: I
authors.lastname: Kinoshita
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Shimizu
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Ohba
authors.forename: Tomoo
authors.initials: T
authors.lastname: Itoh
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Shichinohe
authors.forename: Hirotoshi
authors.initials: H
authors.lastname: Dosaka-Akita
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D000236:Adenoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D001665:Binding Sites / Q000235:genetics; D002471:Cell Transformation, Neoplastic; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004268:DNA-Binding Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D020783:Matrix Metalloproteinase 7 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008875:Middle Aged; D009367:Neoplasm Staging; D010766:Phosphorylation; D011485:Protein Binding / Q000235:genetics; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000073940:Transcription Factor 4; D018808:Transcription Factor AP-1 / Q000737:chemistry / Q000378:metabolism; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015533:Transcriptional Activation; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D004268:DNA-Binding Proteins; D016755:Proto-Oncogene Proteins c-jun; C532096:TCF4 protein, human; D000073940:Transcription Factor 4; D018808:Transcription Factor AP-1; D014157:Transcription Factors; D051176:beta Catenin; C060932:MMP7 protein, human; D020783:Matrix Metalloproteinase 7