| Background and Objective: Wnt signaling pathway plays important roles in regulating cell proliferation anddifferentiation by initiating Wnt signaling, transferring signaling and trigering targetgenes transcription. This pathway is a considerable complex system that involvesmultiple interacting fsctors. A good body of evidence revealed that Wnt signalingpathway participates not only in development but also in tumogeneration andprogression. Recent studies have revealed that the most important and representativefactors including as following: 1) Wnts are a family of glycosylated ligands (morethan 16 mammalian family members) that initiate the Wnt pathway. Among these Wntsligands, Wnt2 is closely associated with cell proliferation. The Wnts bind Frizzledreceptors and then transfer signaling from extracellular to intracellular and activatesignaling. 2) β-catenin is a multifunctional protein that is critical for intercellularadhesion through binding of E-cadherin. However, β-catenin is also an integral part ofthe Wnt signaling pathway. After activation of Wnt signaling, β-catenin is not targetedfor ubiquitination and degradation in the proteosome because of inhibition ofGSK3/APC activity. Accumulation of cytoplasmic β-catenin can shift to nucleus andactivates transcription of a series of genes by binding with TCF/LEF. Consequently,β-catenin has been regarded as a pivotal element in Wnt signaling. 3) TCF- β-catenincomplexes bind to DNA and activate Wnt target genes involved in cell cycle andapoptosis, growth factor, cell adhesion etc. CD44 and MMPs are the most importanttarget genes involved in tumor progression. The presence of Wnt pathway in tumorigenesis and progression has been analysed;however, these studies have revealed great differences in results and conclusions usingtumor cell lines, animal models or surgical specimens. It is known that the geographicaldistribution differs in different cancers. For example, a large body of studies more focusedon mammary cancer and colorectal cancer than gastric cancer (GC) in occident. However,GC is one of the most common malignancies and the major cause of cancer-related deathsin China because of its strong tendency of local invasiveness and distal metastasis.Therefore the roles of Wnt pathway in GC have been drawn researchers' attention.Accumulating evidences have demonstrated that translocated β-catenin is commonlyobserved in GC, indicating the Wnt signaling pathway as a contributor to gastriccarcinogenesis. However, few studies were focused on the correlation of altered β-catenindistribution with the depth of cancer invasion and the results are still controversial.Additionally, the investigations concerning the effectors of Wnt signaling have beenperformed separately in gastric cancers. Furthermore, the expression of Wnt and TCF inGC and the correlation with the biological behaviors of GC cell are still known less. To address those issues, a comprehensive investigation was conducted here indifferent gastric tissues (noncancerous mucosa, premalignant and GC tissues) and 4 GCcell lines. GC types were classified histologically as intestinal type or diffuse typeaccording to the Lauren system. We searched for the altered expression of the Wntcomponents (Wnt2, β-catenin, TCF4 and CD44v6) using the same samples andanalysed the correlation between the Wnt signaling pathway and tumor dissemination.The aim is to get the more convinced data about the roles of Wnt signaling in GCcarcinogenesis and progression. It is valuable in the study of mechanism, diagnosis,prognosis and treatment of GC. Materials and methods The surgical speciments and GC cell lines were selected from the gastric tissuebank of cancer institude, Dalian Medical University. By the methods of frozen/paraffintissue array-based immunohistochemistry, western blot and RT-PCR, a paralleled studywas conducted to check the expression of Wnt2, β-catenin, E-cadherin, TCF4 andCD44v6 in GC. The mutation of β-catenin in Exon 3 was detected using PCR-SSCPfollowed by DNA sequencing. The Kruskal-Wallis test, Mann Wh... |
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