Journal Article

REG Iα protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells

Akira Sekikawa, Hirokazu Fukui, Shigehiko Fujii, Kazuhito Ichikawa, Shigeki Tomita, Johji Imura, Tsutomu Chiba and Takahiro Fujimori

in Carcinogenesis

Volume 29, issue 1, pages 76-83
Published in print January 2008 | ISSN: 0143-3334
Published online November 2007 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/bgm250
REG Iα protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells

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Signal transducer and activator of transcription 3 (STAT3) signaling plays roles in inflammation-associated carcinogenesis. Regenerating gene (REG) Iα protein, an interleukin (IL)-6-inducible gene, is suggested to be involved in the gastritis–gastric cancer sequence. We investigated the involvement of IL-6/STAT3 signaling in REG Iα protein expression and examined whether REG Iα protein mediates an anti-apoptotic effect of STAT3 signaling in gastric cancer cells. The effects of IL-6/STAT3 signaling on REG Iα protein expression were examined using a STAT3 small interfering RNA system in gastric cancer cells. The element responsible for IL-6-induced REG Iα promoter activation was determined by a promoter deletion assay. The anti-apoptotic effects of STAT3 signaling and its induced REG Iα protein were examined by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphatase nick-end labeling and caspase assay in vitro. Human gastric cancer specimens were analyzed by immunohistochemistry for phosphorylated signal transducer and activator of transcription 3 (p-STAT3) and REG Iα protein. IL-6 treatment enhanced the expression of REG Iα protein through STAT3 activation in gastric cancer cells. The IL-6-responsive element was determined to lie in the sequence from −142 to −134 of the REG Iα promoter region. REG Iα protein mediated the anti-apoptotic effects of STAT3 signaling in gastric cancer cells by enhancing Akt activation, Bad phosphorylation and Bcl-xL expression. The expression of REG Iα protein was significantly correlated with that of p-STAT3 in gastric cancer tissues. REG Iα protein may play a pivotal role in anti-apoptosis in gastric tumorigenesis under STAT3 activation.

Journal Article.  5566 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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