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首页> 外文期刊>Oncogene >|[beta]|-catenin inhibits cell growth of a malignant mesothelioma cell line, NCI-H28, with a 3p21.3 homozygous deletion
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|[beta]|-catenin inhibits cell growth of a malignant mesothelioma cell line, NCI-H28, with a 3p21.3 homozygous deletion

机译：|β|-连环蛋白抑制具有3p21.3纯合缺失的恶性间皮瘤细胞系NCI-H28的细胞生长

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We have found that a malignant mesothelioma cell line, NCI-H28, had a chromosome 3p21.3 homozygous deletion containing the -catenin gene (CTNNB1), which suggested that the deletion of -catenin might have a growth advantage in the development of this tumor. To determine whether -catenin has a growth-inhibitory activity, we transfected wild-type -catenin, Ser37Cys mutant -catenin as an activated type, and C-terminus deletion mutant -catenin that lacks the transcription activity, into the NCI-H28 cells. A non-small cell lung cancer cell line, NCI-H1299, which expressed endogenous -catenin, was also studied. We tested the localization of exogenous -catenin in the NCI-H28 cells with immunofluorescence, and found that the wild-type -catenin and the C-terminus deletion mutant were more strongly expressed in the plasma membrane and cytoplasm than in the nucleus, while the Ser37Cys mutant was more in the nucleus than in the cytoplasm. By using luciferase-reporter assay, the -catenin/T-cell factor 4-mediated transactivity of the Ser37Cys mutant was shown to be higher than that of the wild-type -catenin in both cell lines. However, the transactivity of the C-terminus deletion mutant was strongly reduced in both. Colony formation of the NCI-H28 cells was reduced by 50% after transfection with the wild-type -catenin, and 60% with the Ser37Cys mutant, but only 20% with the C-terminus deletion mutant compared to the vector control. Inhibition of colony formation in NCI-H28 cells was because of apoptosis, manifested by positive staining of Annexin V and TUNEL assays in transfected cells. In contrast, when transfected with the wild-type -catenin, no significant reduction in colony formation was seen in -catenin wild-type NCI-H1299 cells. In conclusion, our data indicate that inactivation of -catenin by a 3p21.3 homozygous deletion might be a crucial event in the development of the mesothelioma NCI-H28 cells. Thus, while -catenin is well known to be a positive growth-stimulating factor for many human cancers, it can also act as a potential growth suppressor in some types of human cancer cells.
机译：我们发现恶性间皮瘤细胞系NCI-H28具有包含-catenin基因（CTNNB1）的3p21.3染色体纯合缺失，这表明-catenin的缺失可能在这种肿瘤的发展中具有生长优势。为了确定-catenin是否具有生长抑制活性，我们将野生型-catenin，Ser37Cys突变体-catenin作为活化型和C-末端缺失突变体-catenin缺乏转录活性，将其转染到NCI-H28细胞中。还研究了表达内源性连环蛋白的非小细胞肺癌细胞系NCI-H1299。我们用免疫荧光测试了NCI-H28细胞中外源性-catenin的定位，发现野生型-catenin和C端缺失突变体在质膜和细胞质中的表达比在细胞核中更强，而Ser37Cys突变体在细胞核中比在细胞质中更多。通过荧光素酶报告基因测定，在两种细胞系中，Ser37Cys突变体的-catenin / T细胞因子4介导的转运活性均高于野生型-catenin。但是，C-末端缺失突变体的交易性都大大降低了。与载体对照相比，野生型-catenin转染后NCI-H28细胞的集落形成减少了50％，Ser37Cys突变体减少了60％，而C端缺失突变体仅减少了20％ 。 NCI-H28细胞中集落形成的抑制是由于细胞凋亡，其表现为转染细胞中膜联蛋白V和TUNEL检测的阳性染色。相反，当用野生型-catenin转染时，在-catenin野生型NCI-H1299细胞中未观察到菌落形成的显着减少。总之，我们的数据表明，通过3p21.3纯合缺失使-catenin失活可能是间皮瘤NCI-H28细胞发育中的关键事件。因此，尽管众所周知，-catenin是许多人类癌症的积极生长刺激因子，但它也可以在某些类型的人类癌细胞中充当潜在的生长抑制剂。

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