Soldes O S, Kuick R D, Thompson I A, Hughes S J, Orringer M B, Iannettoni M D, Hanash S M, Beer D G
Department of Surgery, University of Michigan Medical Center, Ann Arbor 48109, USA.
Br J Cancer. 1999 Feb;79(3-4):595-603. doi: 10.1038/sj.bjc.6690094.
The protein expression patterns of normal, metaplastic and malignant oesophageal tissues were analysed by two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) to identify changes associated with Barrett's metaplasia and transformation to oesophageal adenocarcinoma. Heat-shock protein 27 (Hsp27), a small heat-shock protein which is protective against cytotoxic stresses, was abundant in normal oesophagus. However, Hsp27 expression was markedly lower in Barrett's metaplasia and oesophageal adenocarcinomas. This was confirmed by immunohistochemical analysis. Hsp27 protein was most highly expressed in the upper layers of squamous epithelium and exhibited a pattern of expression that corresponded with the degree of squamous maturation. Northern and Southern analysis demonstrated Hsp27 to be regulated at the level of mRNA transcription or abundance. Normal oesophageal tissues were examined for gender differences in Hsp27 expression. Women expressed fourfold higher levels of Hsp27 mRNA, however, this difference was not appreciable in protein expression. Hsp27 protein was inducible by heat shock in Barrett's adenocarcinoma cell lines and an immortalized oesophageal epithelial cell line (HET-1A), but not by oestradiol. These results demonstrate abundant constitutive expression of the stress-response protein Hsp27 in the normal oesophagus, and suggest that low-level expression in Barrett's metaplasia may be one factor which may influence susceptibility to oesophageal adenocarcinoma development.
通过二维聚丙烯酰胺凝胶电泳（2D-PAGE）分析正常、化生和恶性食管组织的蛋白质表达模式，以确定与巴雷特化生及向食管腺癌转化相关的变化。热休克蛋白27（Hsp27）是一种对细胞毒性应激具有保护作用的小热休克蛋白，在正常食管中含量丰富。然而，Hsp27在巴雷特化生和食管腺癌中的表达明显较低。免疫组织化学分析证实了这一点。Hsp27蛋白在鳞状上皮上层表达最高，其表达模式与鳞状成熟程度相对应。Northern和Southern分析表明Hsp27在mRNA转录或丰度水平受到调控。检测正常食管组织中Hsp27表达的性别差异。女性表达的Hsp27 mRNA水平高四倍，然而，这种差异在蛋白质表达中并不明显。Hsp27蛋白在巴雷特腺癌细胞系和永生化食管上皮细胞系（HET-1A）中可被热休克诱导，但不能被雌二醇诱导。这些结果表明应激反应蛋白Hsp27在正常食管中大量组成性表达，并提示巴雷特化生中低水平表达可能是影响食管腺癌发生易感性的一个因素。
