Department of Basic Oncology, Hacettepe University Cancer Institute, Ankara, Turkey.
Hacettepe University Transgenic Animal Technologies Research and Application Center, Ankara, Turkey.
In Vivo. 2023 Jul-Aug;37(4):1576-1583. doi: 10.21873/invivo.13242.
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).
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.
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.
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.
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。
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。
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。
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。
