Cancer Biology Laboratory, School of Biosciences, University of Kent, Canterbury, Kent CT2 7NJ, UK.
Endocr Relat Cancer. 2010 Dec 13;18(1):39-49. doi: 10.1677/ERC-10-0112. Print 2011 Feb.
The neuregulin 4 gene encodes at least five different variants (designated A1, A2, B1, B2 and B3) produced as a result of alternative splicing. We have determined their sites of expression in normal human adult tissues using isoform-specific antibodies. Their expression is cell type specific and differs in subcellular location suggesting that they may have varied functions in these contexts. We have shown in a panel of prostate cancers that each form is present to differing degrees, and that principal component analysis indicates that there are three patterns of expression. Some isoforms were positively correlated with high prostate-specific antigen levels and others were inversely associated with Gleason score. Synthetic, refolded A forms promoted lamellipodia and filopodia formation in cells expressing the ErbB4 (CTa) receptor and stimulated cell motility in wound healing assays. The data suggest that the different forms have varied sites of expression and function, and this includes effects on cell architecture and motility.
神经调节蛋白 4 基因编码至少五种不同的变体（分别指定为 A1、A2、B1、B2 和 B3），这些变体是通过选择性剪接产生的。我们使用同种型特异性抗体确定了它们在正常成人组织中的表达部位。它们的表达具有细胞类型特异性，并且亚细胞定位不同，表明它们在这些情况下可能具有不同的功能。我们在一系列前列腺癌中表明，每种形式的存在程度不同，主成分分析表明存在三种表达模式。一些同种型与高前列腺特异性抗原水平呈正相关，而其他同种型与 Gleason 评分呈负相关。合成的、重折叠的 A 形式促进表达 ErbB4（CTa）受体的细胞中片状伪足和丝状伪足的形成，并在伤口愈合测定中刺激细胞迁移。这些数据表明，不同的形式具有不同的表达和功能部位，包括对细胞结构和运动的影响。
