Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, PR China.
Oncol Rep. 2010 Jun;23(6):1569-76. doi: 10.3892/or_00000797.
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.
Peutz-Jeghers 综合征（PJS）错构瘤的癌前潜能尚未确定。负责 PJS 的主要基因是 LKB1。LKB1 在细胞中有复杂的作用，因此，LKB1 在 PJS 错构瘤中的确切作用特别难以理解。最近发现，LKB1 在 Xenopus 的早期发育过程中在 Wnt 途径中发挥作用。异常的β-catenin 表达，即激活的 Wnt/β-catenin 信号通路的关键调节因子，似乎在肠肿瘤发生中刺激干扰素诱导基因 1（IFITM1）产物。两者都有助于肠道肿瘤的形成和肿瘤的进展。本研究旨在使用 RT-PCR 和免疫组织化学方法研究 LKB1、β-catenin 和 IFITM1 在 PJS、结直肠腺瘤（CRA）、结直肠癌（CRC）和正常结直肠黏膜（NC）中的表达。免疫荧光用于评估β-catenin 和 IFITM1 的共表达特征。结果表明，在 mRNA 和蛋白水平上，PJSs 的 LKB1、β-catenin 和 IFITM1 的表达谱与 CRA 相似。肿瘤细胞中β-catenin 的细胞质水平与 LKB1 和 IFITM1 的表达密切相关。在大多数（16/20）PJS 息肉中发现了β-catenin 的失调。免疫荧光还显示 PJS 中的β-catenin 和 IFITM1 在细胞质中共表达。这些发现表明，Wnt 信号可能在 PJS 的一个亚群中被激活，并且 PJS 息肉中 Wnt/β-catenin 信号的激活可能是由 LKB1 表达引起的。激活的β-catenin 信号通路包括 IFITM1，可能在 PJS 息肉的一个亚群中发挥重要作用。
