RRC ID 42685
Author Uchiyama S, Itoh H, Naganuma S, Nagaike K, Fukushima T, Tanaka H, Hamasuna R, Chijiiwa K, Kataoka H.
Title Enhanced expression of hepatocyte growth factor activator inhibitor type 2-related small peptide at the invasive front of colon cancers.
Journal Gut
Abstract BACKGROUND:Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a small nuclear protein abundantly expressed in the gastrointestinal epithelium. However, its functions remain unknown.
AIMS:To investigate the expression and localisation of H2RSP in normal, injured and neoplastic human intestinal tissue.
METHODS:Immunohistochemical examination and in situ hybridisation for H2RSP were performed using normal and diseased intestinal specimens. Its subcellular localisation and effects on the cellular proliferation and invasiveness were examined using cultured cells.
RESULTS:In the normal intestine, H2RSP was observed in the nuclei of surface epithelial cells and this nuclear localisation was impaired in regenerating epithelium. In vitro, the nuclear translocation of H2RSP was observed along with increasing cellular density, and an overexpression of H2RSP resulted in a reduced growth rate and enhanced invasiveness. H2RSP expression was down regulated in well-differentiated colorectal adenocarcinomas. However, a marked up regulation of the cytoplasmic H2RSP immunoreactivity was observed in cancer cells at the invasive front. These cells showed low MIB-1 labelling, an enhanced p16 expression and nuclear beta-catenin. The number of H2RSP-positive cells in the invasive front of well-differentiated adenocarcinomas was considerably higher in the cases with lymph node metastases than in node-negative ones.
CONCLUSION:In the normal intestine, the nuclear accumulation of H2RSP is a marker of differentiated epithelial cells. Although H2RSP was down regulated in colorectal adenocarcinomas, a paradoxical up regulation was observed in actively invading carcinoma cells. H2RSP immunoreactivity at the invasive front may serve as a marker of invasive phenotype of well-differentiated colon cancers.
Volume 56(2)
Pages 215-26
Published 2007-2
DOI 10.1136/gut.2005.084079
PII gut.2005.084079
PMID 16809422
PMC PMC1856747
MeSH Adenocarcinoma / chemistry* Adenocarcinoma / immunology Adenocarcinoma / pathology Adenoma / chemistry Adenoma / immunology Adenoma / pathology Animals CHO Cells Cell Count Cell Differentiation / physiology Cell Division / physiology Cell Line, Tumor Colitis, Ulcerative / immunology Colitis, Ulcerative / pathology Colonic Neoplasms / chemistry* Colonic Neoplasms / immunology Colonic Neoplasms / pathology Colorectal Neoplasms / chemistry Colorectal Neoplasms / immunology Colorectal Neoplasms / pathology Cricetinae Cricetulus Epithelial Cells / chemistry Epithelial Cells / immunology Epithelial Cells / pathology Humans Hyperplasia Immunohistochemistry / methods In Situ Hybridization / methods Intestinal Polyps / chemistry Intestinal Polyps / immunology Intestinal Polyps / pathology Intestines / chemistry Intestines / immunology Intestines / pathology Lymphatic Metastasis Neoplasm Invasiveness Neoplasm Proteins / analysis* Neoplasm Proteins / immunology Nuclear Proteins / analysis* Nuclear Proteins / immunology Transcription Factors / analysis* Transcription Factors / immunology beta Catenin / analysis
IF 17.016
Times Cited 3
Human and Animal Cells