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结直肠癌中磷酸化β-连环蛋白的亚细胞分布特征。

Characterization of the Subcellular Distribution of Phospho-β-catenin in Colorectal Cancer.

机构信息

Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.

Hacettepe University Transgenic Animal Technologies Research and Application Center, Ankara, Turkey.

出版信息

In Vivo. 2023 Jul-Aug;37(4):1576-1583. doi: 10.21873/invivo.13242.

Abstract

BACKGROUND/AIM: β-Catenin is a multifunctional protein, which is localized to different subcellular compartments of the normal colon epithelium. The hyperactivation of Wnt pathway results in the nuclear accumulation of β-catenin and induction of colorectal carcinogenesis. Although N-terminally hypo-phosphorylated β-catenin (active β-catenin) is known as the transcriptionally active form, phospho-S33/S37/T41-β-catenin (phospho-β-catenin) can also accumulate in the nucleus. In this study, we aimed to characterize the subcellular distribution of phospho-β-catenin and the other forms of β-catenin in normal colon epithelium and colorectal cancer (CRC).

MATERIALS AND METHODS

Phosphorylated, hypo-phosphorylated, and the total pool of β-catenin were evaluated in colon epithelium and CRC using immunohistochemistry, immunofluorescence staining, and western blotting. Tissue microarrays were used to determine the expression pattern of phospho-β-catenin in CRC samples.

RESULTS

Almost 11% (49/452) of CRCs expressed moderate to high levels of phospho-β-catenin in the nucleus. In addition, hypo-phosphorylated and phosphorylated forms of β-catenin localized to different subcellular regions in normal colon epithelium and CRC. Immunoblotting experiments suggested that truncated phospho-β-catenin forms can be found in CRCs.

CONCLUSION

Phospho-β-catenin accumulates in the nucleus and different molecular weight β-catenin proteins are present in colon cancer cells. To elaborate on the functional significance of nuclear phospho-β-catenin, further studies should be performed.

摘要

背景/目的:β-连环蛋白是一种多功能蛋白,其在正常结肠上皮细胞的不同亚细胞区室中定位。Wnt 通路的过度激活导致β-连环蛋白核内积聚,并诱导结直肠肿瘤发生。虽然 N 端低磷酸化的 β-连环蛋白(活性 β-连环蛋白)被认为是转录活性形式,但磷酸化 S33/S37/T41-β-连环蛋白(磷酸化-β-连环蛋白)也可以在核内积聚。在本研究中,我们旨在研究磷酸化-β-连环蛋白和其他形式的β-连环蛋白在正常结肠上皮和结直肠癌(CRC)中的亚细胞分布。

材料和方法

使用免疫组织化学、免疫荧光染色和 Western blot 检测结肠上皮和 CRC 中磷酸化、低磷酸化和总β-连环蛋白的表达。组织微阵列用于确定 CRC 样本中磷酸化-β-连环蛋白的表达模式。

结果

将近 11%(49/452)的 CRC 细胞核中表达中等至高水平的磷酸化-β-连环蛋白。此外,在正常结肠上皮和 CRC 中,β-连环蛋白的低磷酸化和磷酸化形式定位于不同的亚细胞区域。免疫印迹实验表明,CRC 中存在截断的磷酸化-β-连环蛋白形式。

结论

磷酸化-β-连环蛋白在核内积聚,并且在结肠癌细胞中存在不同分子量的β-连环蛋白蛋白。为了详细阐明核内磷酸化-β-连环蛋白的功能意义,应进一步开展研究。

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