Analysis of beta-catenin gene in gastric cancer cells

胃癌细胞β-catenin基因分析

• 批准号: 07670605
• 负责人: KATO Junji
• 金额: $ 1.47万
• 依托单位: SAPPORO MEDICAL UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1995
• 资助国家: 日本
• 起止时间: 1995 至 1996
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670605/
• 关键词: gastric cancer; adhesion; cadherin; catenin; cell cycle; cdk inhibitor; p21; p27; E-cadherin; β-catenin; スキルス胃癌; adherence junction; transfection; Southern blot

Detachment of cell-cell adhesion is indispensable for the first step of invasion and metastasis of cancer cells. We have recently demonstrated that the function of E-cadherin was completely abolished in HSC-39, despite the high expression of E-cadherin, because of mutations in one of the E-cadherin-associated cytoplasmic proteins ; beta-catenin. In the present study, we firstly investigated beta-catenin gene expression in various human gastric cancer cells. It was revealed that a gastric carcinoma cell line KATO-III expressed the rearranged beta-catenin gene with amplification. Recently, it has been reported that beta-catenin binds to both APC and ErbB-2. Thus the function of E-cadherin system is supposed to affect the cell proliferation as well as cell-cell adhesion. We then transfected a wild-type beta-catenin gene expression vector into HSC-39 cells to examine the beta-catenin-mediated signal transduction. E-cadherin dependent cell-cell adhesiveness was recovered by the transfection of wild-type beta-catenin cDNA as revealed by cell compaction, cell-aggregation and immunofluorescence staining. In HSC-39beta cells, the cell proliferation, anchorageindependent growth and tumorigenecity were significantly reduced as comared with those of parental cells. Furthermore, the expressions of p21^<Cip1> and p27^<Kip1>, which inhibit the progression of cell cycle from G1 to S phase, were remarkably increased in HSC-39/beta. These results suggested that beta-catenin is involved in the cell cycle regulation as well as E-cadherin dependent cell-cell adhesion system.

细胞间粘附的脱离是癌细胞侵袭和转移的第一步。我们最近证明，尽管E-钙粘蛋白的高表达，但在HSC-39中E-钙粘蛋白的功能被完全消除，这是因为E-钙粘蛋白相关的胞质蛋白之一β-连环蛋白发生突变。在本研究中，我们首先研究了β-连环蛋白基因在各种人胃癌细胞中的表达。结果显示，胃癌细胞系KATO-III扩增表达重排的β-连环蛋白基因。最近，已经报道β-连环蛋白结合APC和ErbB-2。因此，E-cadherin系统的功能可能影响细胞增殖和细胞间粘附。然后，我们将野生型β-连环蛋白基因表达载体转染入HSC-39细胞，以检查β-连环蛋白介导的信号转导。通过转染野生型β-连环蛋白cDNA恢复E-钙粘蛋白依赖性细胞-细胞粘附，如通过细胞压实、细胞聚集和免疫荧光染色所揭示的。HSC-39 β细胞的增殖能力、非贴壁生长能力和致瘤性均明显低于亲本细胞。此外，<Cip1><Kip1>抑制细胞从G1期向S期进展的p21^和p27^的表达在HSC-39/β中显著增加。这些结果提示β-catenin参与细胞周期调控以及E-cadherin依赖的细胞-细胞粘附系统。

项目成果

松浦邦彦 他: "スキルス胃癌と線維化" メディカル用語ライブラリー消化器疾患. 124-125 (1996)

Kunihiko Matsuura 等人：“硬性胃癌和纤维化”医学术语库胃肠疾病 124-125 (1996)。

Kawanishi J,Kato J., Sasaki K,Fujii S,Watanabe N,Niitsu, Y.: "Loss of E-cadherin dependent cell-cell adhesion due to mutation of beta-catenin gene in a human cancer cell line HSC-39." Molecular Cellular Biology. 15. 1175-1181 (1995)

Kawanishi J、Kato J.、Sasaki K、Fujii S、Watanabe N、Niitsu、Y.：“由于人类癌细胞系 HSC-39 中 β-连环蛋白基因突变，导致 E-钙粘蛋白依赖性细胞间粘附丧失。

Kawanishi J,et al: "Loss of E-cadherin dependent cell-cell adhesion due to mutation of β-catenin gene in a human cancer cell line HSC-39" Molecular and Cellular Biology. 15. 1175-1181 (1995)

Kawanishi J 等人：“由于人癌细胞系 HSC-39 中 β-连环蛋白基因突变而导致 E-钙粘蛋白依赖性细胞间粘附丧失”，《分子与细胞生物学》15. 1175-1181 (1995)。

加藤淳二 他: "胃癌細胞HSC-39にみられたE-cadherin依存性細胞接着機能消失機構:新たな機序としてのβ-カテニン遺伝子異常" 小俣政男監修:細胞内遺伝子導入と消化器疾患. 105-113 (1995)

Junji Kato等：“在胃癌细胞HSC-39中观察到的E-cadherin依赖性细胞粘附丧失机制：β-catenin基因异常作为新机制”Masao Omata监督：细胞内基因转移和胃肠道疾病105-113。 (1995)

Kawanishi J,Kato J,Sssaki K,Watanabe N,Niitsu Y.: "Dysfunction of E-cadherin due to mutation of beta-catenin in a scirrhous gastric cancer cell line" Japanese Journal of Clinical Medicine. 53. 1590-1594 (1995)

Kawanishi J，Kato J，Sssaki K，Watanabe N，Niitsu Y.：“硬质胃癌细胞系中β-连环蛋白突变导致的 E-钙粘蛋白功能障碍”日本临床医学杂志。