摘要
雌激素受体 (ERα)在乳腺癌的发生发展过程中起重要作用。在乳腺癌中 ,人X盒结合蛋白 1(XBP 1)与ERα共表达 ,并在一些乳腺肿瘤中过表达。最近发现XBP 1有两种剪切形式 ,即XBP 1S和XBP 1U ,但它们在乳腺癌细胞中的表达形式和在ERα信号途径中的作用还不清楚。采用RT PCR技术 ,检测到XBP 1的两种剪切形式在正常乳腺细胞株和不同乳腺癌细胞株中均表达。利用ERE LUC报告基因 ,检测XBP 1S和XBP 1U在乳腺癌细胞株MDA MB 4 35中对ERα转录活性的影响表明 ,它们均以激素不依赖但以XBP 1剂量依赖的形式提高ERα的转录活性 ,XBP 1S的活性高于XBP 1U。XBP 1S和XBP 1U高效提高ERE LUC报告基因的活性依赖于ERα的存在。结果提示 ,XBP 1S和XBP 1U可能通过ERα信号途径在乳腺癌的发生发展中起重要作用。
Estrogen receptor (ERα) plays an important role in the development and progression of breast cancer.Several recent studies have demonstrated that expression of human X-box binding protein 1 (XBP-1) is associated with ERα status in breast tumors and overexpressed in a subset of breast tumors.XBP-1 has two splicing variants,which were designated as XBP-1S and XBP-1U,respectively.However,little is known about the expression pattern of XBP-1S and XBP-1U in breast cancer cells and about their roles in ERα signaling.In this study,the expression of two splicing forms of XBP-1 was detected in breast cancer cell lines with RT-PCR.Estrogen response element (ERE)-containing luciferase reporter assay was used to determine the effects of XBP-1S and XBP-1U on the transcription activity of ERα in MDA-MB-435 breast cancer cells.The result showed that both XBP-1S and XBP-1U enhanced the transcription activity of ERα in a hormone-independent and dose-dependent manner and the activity of of XBP-1S is higher than that of XBP-1U.Enhancement of ERE-containing luciferase reporter gene expression by XBP-1S and XBP-1U was dependent on ERα.These data suggest that XBP-1S and XBP-1U may play important roles in breast cancer growth and progression through ERα signaling.
基金
军事医学科学院创新基金
福建省百千万人才工程资助项目~~
