Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning 110004, P.R. China.
Department of Ultrasound, Shengjing Hospital Affiliated to China Medical University, Shenyang, Liaoning 110004, P.R. China.
Int J Mol Med. 2017 Aug;40(2):293-302. doi: 10.3892/ijmm.2017.3009. Epub 2017 Jun 2.
MUC1 is a type I transmembrane glycoprotein and is overexpressed in various epithelial tumor tissues. Some researchers have demonstrated that the glycosylation status of MUC1 can affect MUC1-mediated tumor growth and cell differentiation. In our previous study, we proved that the abilities of cell proliferation, adhesion, invasion and metastasis, and drug resistance were enhanced in ovarian cancer cells stably expressing Lewis(y). Therefore, we hypothesized that Lewis(y) antigen may play a central role in regulating MUC1 expression, and MUC1-mediated cell growth and differentiation may be closely associated with Lewis(y) antigen. This study aimed to examine the correlation between MUC1 expression and Lewis(y) antigen levels in ovarian cancer cell lines and tissue samples. A series of techniques, including RT-qPCR, western blot anlaysis, immunoprecipitation, immunohistochemistry and double-labeling immunofluorescence were applied to detect the expression of Lewis(y) and MUC1. In malignant epithelial ovarian tumors, the positive expression rates of Lewis(y) antigen and MUC1 were 88.33 and 86.67%, respectively, which were markedly higher than those in borderline (60.00 and 53.33%, P<0.05), benign (33.33 and 30%, P<0.01) and normal (0 and 25%, P<0.01) ovarian samples. There was no correlation between the positive expression rates of Lewis(y) or MUC1 and clinicopathological parameters in ovarian cancers (P>0.05). The expression levels of Lewis(y) and MUC1 correlated with the clinical FIGO stage (P<0.05). Both MUC1 and Lewis(y) were highly expressed in ovarian cancer tissues, and their expression levels were positively correlated (P<0.01). In α1,2-fucosyltransferase (α1,2-FT)-transfected cells, the gene and protein expression levels of MUC1 were significantly upregulated compared with the cells that did not overexpress α1,2-FT (P<0.05). The ratio of Lewis(y) immunoprecipitated with MUC1 to total MUC1 increased 1.55-fold in α1,2-FT-overexpressing cells (P<0.05). The overexpression of Lewis(y) resulted in the upregulation of MUC1. On the whole, our data indicate that both MUC1 and Lewis(y) are associated with the occurrence and development of ovarian cancers.
MUC1 是一种 I 型跨膜糖蛋白,在各种上皮肿瘤组织中过度表达。一些研究人员已经证明,MUC1 的糖基化状态可以影响 MUC1 介导的肿瘤生长和细胞分化。在我们之前的研究中,我们证明了在稳定表达 Lewis(y)的卵巢癌细胞中,细胞增殖、黏附、侵袭和转移以及耐药能力增强。因此,我们假设 Lewis(y)抗原可能在调节 MUC1 表达中起核心作用,并且 MUC1 介导的细胞生长和分化可能与 Lewis(y)抗原密切相关。本研究旨在检查卵巢癌细胞系和组织样本中 MUC1 表达与 Lewis(y)抗原水平之间的相关性。应用一系列技术,包括 RT-qPCR、western blot 分析、免疫沉淀、免疫组织化学和双标记免疫荧光,检测 Lewis(y)和 MUC1 的表达。在恶性上皮性卵巢肿瘤中,Lewis(y)抗原和 MUC1 的阳性表达率分别为 88.33%和 86.67%,明显高于交界性肿瘤(60.00%和 53.33%,P<0.05)、良性肿瘤(33.33%和 30%,P<0.01)和正常卵巢组织(0%和 25%,P<0.01)。在卵巢癌中,Lewis(y)或 MUC1 的阳性表达率与临床病理参数无关(P>0.05)。Lewis(y)和 MUC1 的表达水平与临床 FIGO 分期相关(P<0.05)。MUC1 和 Lewis(y)在卵巢癌组织中均高表达,且表达水平呈正相关(P<0.01)。在 α1,2-岩藻糖基转移酶(α1,2-FT)转染细胞中,与未过表达 α1,2-FT 的细胞相比,MUC1 的基因和蛋白表达水平显著上调(P<0.05)。在α1,2-FT 过表达细胞中,与总 MUC1 免疫沉淀的 Lewis(y)与 MUC1 的比值增加了 1.55 倍(P<0.05)。Lewis(y)的过表达导致 MUC1 的上调。总的来说,我们的数据表明 MUC1 和 Lewis(y)均与卵巢癌的发生和发展有关。