RRC ID 43861
Author Mao W, Chen J, Peng TL, Yin XF, Chen LZ, Chen MH.
Title Downregulation of gastrokine-1 in gastric cancer tissues and restoration of its expression induced gastric cancer cells to apoptosis.
Journal J. Exp. Clin. Cancer Res.
Abstract BACKGROUND:Gastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells.
METHODS:RT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes.
RESULTS:Significant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes.
CONCLUSIONS:Expression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.
Volume 31
Pages 49
Published 2012-5-23
DOI 10.1186/1756-9966-31-49
PII 1756-9966-31-49
PMID 22621392
PMC PMC3511871
MeSH Adult Aged Apoptosis / drug effects Cell Line, Tumor Cell Survival Epithelium / metabolism Female Fluorouracil / pharmacology Gastric Mucosa / metabolism Gene Expression Regulation, Neoplastic* Humans Male Middle Aged Neoplasm Staging Peptide Hormones* / genetics Peptide Hormones* / metabolism Stomach Neoplasms* / genetics Stomach Neoplasms* / metabolism Stomach Neoplasms* / pathology
IF 6.217
Times Cited 12
Human and Animal Cells