Oncol Rep 2010 Jun 01;236:1569-76. doi: 10.3892/or_00000797.

Wnt signaling may be activated in a subset of Peutz-Jeghers syndrome polyps closely correlating to LKB1 expression.

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The premalignant potential of Peutz-Jeghers syndrome (PJS) hamartomas has not been established. The major gene responsible for PJS is LKB1. LKB1 has a complex cellular role, therefore, the exact role of LKB1 in Peutz-Jeghers syndrome hamartomas (PJSs) is particularly difficult to understand. It has recently been found that LKB1 functions in the Wnt pathway in Xenopus during early development. Aberrant beta-catenin expression, the key regulator of the activated Wnt/beta-catenin signaling pathway, appears to stimulate interferon-induced gene 1 (IFITM1) products in intestinal tumorigenesis. Both contribute to intestinal tumor formation and tumor progression. This study was designed to investigate expression of LKB1, beta-catenin and IFITM1 in PJSs, colorectal adenomas (CRAs), colorectal carcinomas (CRCs) and normal colorectal mucosas (NCs) using RT-PCR and immunohistochemistry. Immunofluorescence was used to assess the co-expression characteristics of beta-catenin and IFITM1. Results showed that the expression profiles of LKB1, beta-catenin and IFITM1 in PJSs were similar to those in CRAs both at the mRNA and protein levels. The cytoplasmic level of beta-catenin expression correlated strongly with LKB1 and IFITM1 expression in the tumor cells. The dyregulation of beta-catenin was found in a majority (16/20) of the PJS polyps. Immunofluorescence also revealed co-expression of beta-catenin and IFITM1 in the cytoplasm of the PJSs. These findings suggest that Wnt signaling may be activated in a subset of PJSs, and activation of the Wnt/beta-catenin signaling in PJS polyps may be caused by LKB1 expression. The activated beta-catenin signaling pathway including IFITM1 might play an important role in a subset of PJS polyps.

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Species referenced: Xenopus
Genes referenced: ifitm1 stk11