Journal
CANCER LETTERS
Volume 274, Issue 1, Pages 143-150Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.canlet.2008.09.019
Keywords
PTEN; CDX2; Intestinal differentiation; Claudin; Gastric carcinoma
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Funding
- Japan Society for Promotion of Science [C-19590347, C-20590341]
- Terry Fox Run Foundation for Cancer Research
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The PTEN tumor suppressor localizes predominantly to the cytoplasm, where it negatively regulates the phosphatidylinositol 3-kinase-AKT signaling pathway: however, the biological significance of nuclear PTEN in gastric carcinoma (GC) remains unknown. In this study, transduction of recombinant PTEN into GC-derived TMK-1 cells promoted PTEN nuclear localization with increased mRNA levels of CDX2 and intestinal claudins (CLDN3 and CLDN4), whereas the G129E phosphatase 'dead' mutant had no effect. In GC tissue samples, tumors with nuclear PTEN expression frequently demonstrated the intestinal-type claudin phenotype. Our results suggested that nuclear localization of PTEN is important for determining intestinal differentiation of GCs. (c) 2008 Elsevier Ireland Ltd. All rights reserved.
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