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β-连环蛋白的外源性表达调节接触抑制、非锚定依赖性生长、失巢凋亡和辐射诱导的细胞周期停滞。

Exogenous expression of beta-catenin regulates contact inhibition, anchorage-independent growth, anoikis, and radiation-induced cell cycle arrest.

作者信息

Orford K, Orford C C, Byers S W

机构信息

The Lombardi Cancer Center and the Department of Cell Biology, Georgetown University School of Medicine, Washington, District of Columbia 20007, USA.

出版信息

J Cell Biol. 1999 Aug 23;146(4):855-68. doi: 10.1083/jcb.146.4.855.

DOI:10.1083/jcb.146.4.855
PMID:10459019
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2156133/
Abstract

beta-Catenin is an important regulator of cell-cell adhesion and embryonic development that associates with and regulates the function of the LEF/TCF family of transcription factors. Mutations of beta-catenin and the tumor suppressor gene, adenomatous polyposis coli, occur in human cancers, but it is not known if, and by what mechanism, increased beta-catenin causes cellular transformation. This study demonstrates that modest overexpression of beta-catenin in a normal epithelial cell results in cellular transformation. These cells form colonies in soft agar, survive in suspension, and continue to proliferate at high cell density and following gamma-irradiation. Endogenous cytoplasmic beta-catenin levels and signaling activity were also found to oscillate during the cell cycle. Taken together, these data demonstrate that beta-catenin functions as an oncogene by promoting the G(1) to S phase transition and protecting cells from suspension-induced apoptosis (anoikis).

摘要

β-连环蛋白是细胞间黏附及胚胎发育的重要调节因子，它与LEF/TCF转录因子家族相关联并调节其功能。β-连环蛋白和肿瘤抑制基因腺瘤性息肉病基因的突变发生于人类癌症中，但尚不清楚β-连环蛋白增加是否以及通过何种机制导致细胞转化。本研究表明，在正常上皮细胞中适度过表达β-连环蛋白会导致细胞转化。这些细胞在软琼脂中形成集落，在悬浮状态下存活，并在高细胞密度及γ射线照射后继续增殖。还发现内源性细胞质β-连环蛋白水平和信号活性在细胞周期中振荡。综上所述，这些数据表明β-连环蛋白通过促进G1期到S期的转变以及保护细胞免受悬浮诱导的凋亡（失巢凋亡）而发挥癌基因的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb7/2156133/a1df88c06aa5/JCB9812036.f9.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb7/2156133/12aca5f1696d/JCB9812036.f8.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb7/2156133/a1df88c06aa5/JCB9812036.f9.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb7/2156133/b61b5f8ab235/JCB9812036.f1.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb7/2156133/bfb5f9e21a9e/JCB9812036.f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb7/2156133/3176259cd286/JCB9812036.f7.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcb7/2156133/12aca5f1696d/JCB9812036.f8.jpg
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