Mutation of β-catenin and its protein accumulation in solid and cystic tumor of the pancreas associated with metastasis

Miao, Jiangyong; Kusafuka, Takeshi; Kuroda, Seika; Yoneda, Akihiro; Zhou, Zhiwei; Okada, Akira

doi:10.3892/ijmm.11.4.461

Cited by 12 publications

(12 citation statements)

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“…Activation of the Wnt target gene will contribute to the development of cancer in terms of proliferation, invasion and metastasis, and angiogenesis (Taketo, 2006;Neth et al, 2007). Additionally, inhibition of Wnt signalling could reduce cell proliferation and increase apoptosis in pancreatic adenocarcinoma cells (Miao et al, 2003;Pasca di Magliano et al, 2007;Nawroth et al, 2007). Here, the b-catenin/Tcf assay showed that the TOPflash luciferase activity was obviously decreased whereas FOPflash luciferase activity has no change.…”

Section: Discussionmentioning

confidence: 86%

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

et al. 2008

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Extra-pancreatic metastasis is a difficult problem for surgical intervention in pancreatic cancer. CXC chemokine receptor 4 (CXCR4) was considered to have an important role in this process. We hypothesized it may contribute to the pancreatic cancer progression through influencing canonical Wnt pathway. The purpose of this study was to examine the functional role of CXCR4 in the progression of pancreatic cancers and explore the possible mechanism. To this end, the relation between CXCR4 and clinical characteristics was analysed. shRNA against CXCR4 was applied to disrupt the SDF-1/CXCR4 signal transduction pathways in pancreatic cancer cell lines. Our results showed that overall survival in the case of patients positive for CXCR4 expression was significantly lower than that in the case of patients negative for CXCR4 expression. Notably, in vitro studies we observed that the abrogation of CXCR4 could obviously influence the pancreatic cancer cell phenotype including cell proliferation, colony formation, cell invasion and also inhibit the TOPflash activity. In addition, Wnt target genes and mesenchymal markers such as Vimentin and Slug were also inhibited in CXCR4 knockdown cells. Collectively, these data reported here demonstrate CXCR4 could modulate the canonical Wnt pathway and perhaps be a promising therapeutic target for pancreatic cancer progression.

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Section: Discussionmentioning

confidence: 86%

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

et al. 2008

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“…Mutations of CTNBB1 in SPN were first demonstrated in 2001 (7). We reviewed and analyzed the mutations of CTNBB1 in 123 pancreatic SPN cases that retrieved from PubMed search encompassing the years 2001 through 2012 (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). Of these 123 cases, 111 (90.2%) of the patients with pancreatic SPN demonstrated mutations in CTNNB1 exon 3 (Fig.…”

Section: Discussionmentioning

confidence: 99%

Large Solid-pseudopapillary Neoplasm of the Pancreas with Aberrant Protein Expression and Mutation of β-Catenin: A Case Report and Literature Review of the Distribution of β-Catenin Mutation

et al. 2013

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Solid-pseudopapillary neoplasms (SPN) are rare pancreatic tumors. The etiology of SPN involves mutations in the gene that encodes β-catenin (CTNNB1). We herein report the case of a 23-year-old woman with a large SPN with proliferating tumor cells that displayed both solid and pseudo-papillary patterns. The simultaneous nuclear accumulation and loss of membrane localization of β-catenin and E-cadherin was specifically observed in the tumor cells. Further, the tumor cells were shown to harbor a missense mutation in exon 3 of CTNNB1. We also present a review of the literature describing the clustering of CTNNB1 mutations in patients with SPN.

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“…In the pediatric age group, our previous study and that of others found ß-catenin mutations in the majority of hepatoblastoma, solid and cystic tumors of the pancreas, and a number of nephroblastoma (8)(9)(10)15,16,(28)(29)(30). A common feature occurring among these Wnt associated tumors is the nuclear localization of ß-catenin protein, a molecule which plays its central role in modulating the transcription of target oncogenes in the pathway.…”

Section: Discussionmentioning

confidence: 99%

In vitro RNA interference against β-catenin inhibits the proliferation of pediatric hepatic tumors

Sangkhathat

Kusafuka²,

Miao³

et al. 2006

Int J Oncol

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Abstract. Mutations of ß-catenin have been identified in the majority of pediatric hepatic malignancies, including hepatoblastoma (HB) and hepatocellular carcinoma (HCC), suggesting its important contribution in hepatic tumorigenesis in this age group. However, the role of ß-catenin/canonical Wnt signaling pathway in the neoplastic growth of cancer cells has not been directly studied. To address ß-catenin's capability in maintaining the malignant phenotype in established pediatric HB and HCC cell lines, HuH-6 and HepG2, harboring mutated and overexpressed ß-catenin, we carried out a series of in vitro analyses through a transfection of short interfering RNAs (siRNAs) to generate a loss-of-function model. HuH-7, another HB cell line derived from a pediatric patient without a stabilizing mutation was used for comparison. RNA interference successfully manipulated the degradation of overexpressed ß-catenin. In all cell lines, ß-catenin mRNA was suppressed by 80-90% after 48 h of transfection, and a reduction of its protein expression was demonstrated. In HuH-6 and HepG2, the pre-existing ß-catenin nuclear accumulation disappeared and reductions of ß-catenin downstream target genes, c-myc and cyclinD1, were also evidenced after the treatment. The in vitro proliferation of both cell lines was transiently inhibited. In contrast, the suppression of ß-catenin in HuH-7 did not lead to a significant change in the expression of target genes or cellular proliferation. Our data indicate that ß-catenin can be considered a specific target for gene therapy in pediatric hepatic tumors with mutations and overexpression of this gene.

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Mutation of β-catenin and its protein accumulation in solid and cystic tumor of the pancreas associated with metastasis

Cited by 12 publications

References 0 publications

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

Large Solid-pseudopapillary Neoplasm of the Pancreas with Aberrant Protein Expression and Mutation of β-Catenin: A Case Report and Literature Review of the Distribution of β-Catenin Mutation

In vitro RNA interference against β-catenin inhibits the proliferation of pediatric hepatic tumors

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