BACKGROUND AND AIM: Methyl or 1, N(6) -ethenoadenine base lesions are frequent and highly-mutagenic or -carcinogenic events in mammalian DNA. Human AlkB homologue-2 (hABH2), a homologue of the Escherichia coli AlkB protein, has been found to be the principal dioxygenase for the repair of these lesions. Mounting evidence indicates that impaired DNA repair contributes to gastric cancer induction and progression. Whether hABH2 is involved in this malignancy is unknown. The present study was aimed to investigate the expression profile of hABH2 in gastric cancer and the effect of hABH2 on cancer cell growth. METHODS: The expression of hABH2 in 35 pair-matched gastric neoplastic and adjacent non-neoplastic tissues, and in five gastric cancer cell lines, was examined by real-time polymerase chain reaction (PCR), immunohistochemistry, or Western blot. The cell growth was determined using cell-counting kit-8 assay. The apoptosis or cell-cycle analysis was determined using flow cytometry. RESULTS: The hABH2 expression was downregulated in 68% (24/35) of primary gastric cancers, as determined by real-time PCR; the hABH2 expression was also substantially decreased in gastric cancer cell lines. Immunohistochemical or Western blot analysis further confirmed the downregulation of hABH2 expression in gastric cancers. The overexpression of hABH2 significantly inhibited the proliferation of gastric cancer cells, and induced G(1) arrest of the cell cycle, while hABH2 knockdown promoted cell growth and cell-cycle progression of gastric cancer cells. CONCLUSIONS: These results suggest that hABH2 is downregulated in a subset of gastric cancers, and might be involved in the molecular mechanism of gastric cancer through inhibiting the proliferation of gastric cancer cells.
BACKGROUND AND AIM: Methyl or 1, N(6) -ethenoadenine base lesions are frequent and highly-mutagenic or -carcinogenic events in mammalian DNA. Human AlkB homologue-2 (hABH2), a homologue of the Escherichia coli AlkB protein, has been found to be the principal dioxygenase for the repair of these lesions. Mounting evidence indicates that impaired DNA repair contributes to gastric cancer induction and progression. Whether hABH2 is involved in this malignancy is unknown. The present study was aimed to investigate the expression profile of hABH2 in gastric cancer and the effect of hABH2 on cancer cell growth. METHODS: The expression of hABH2 in 35 pair-matched gastric neoplastic and adjacent non-neoplastic tissues, and in five gastric cancer cell lines, was examined by real-time polymerase chain reaction (PCR), immunohistochemistry, or Western blot. The cell growth was determined using cell-counting kit-8 assay. The apoptosis or cell-cycle analysis was determined using flow cytometry. RESULTS: The hABH2 expression was downregulated in 68% (24/35) of primary gastric cancers, as determined by real-time PCR; the hABH2 expression was also substantially decreased in gastric cancer cell lines. Immunohistochemical or Western blot analysis further confirmed the downregulation of hABH2 expression in gastric cancers. The overexpression of hABH2 significantly inhibited the proliferation of gastric cancer cells, and induced G(1) arrest of the cell cycle, while hABH2 knockdown promoted cell growth and cell-cycle progression of gastric cancer cells. CONCLUSIONS: These results suggest that hABH2 is downregulated in a subset of gastric cancers, and might be involved in the molecular mechanism of gastric cancer through inhibiting the proliferation of gastric cancer cells.