Hellman K, Alaiya A A, Becker S, Lomnytska M, Schedvins K, Steinberg W, Hellström A-C, Andersson S, Hellman U, Auer G
Department of Gynaecologic Oncology, Radiumhemmet, Karolinska University Hospital, Stockholm, Sweden.
Br J Cancer. 2009 Apr 21;100(8):1303-14. doi: 10.1038/sj.bjc.6604975. Epub 2009 Mar 24.
The objective was to identify proteins differentially expressed in vaginal cancer to elucidate relevant cancer-related proteins. A total of 16 fresh-frozen tissue biopsies, consisting of 5 biopsies from normal vaginal epithelium, 6 from primary vaginal carcinomas and 5 from primary cervical carcinomas, were analysed using two-dimensional gel electrophoresis (2-DE) and MALDI-TOF mass spectrometry. Of the 43 proteins identified with significant alterations in protein expression between non-tumourous and tumourous tissue, 26 were upregulated and 17 were downregulated. Some were similarly altered in vaginal and cervical carcinoma, including cytoskeletal proteins, tumour suppressor proteins, oncoproteins implicated in apoptosis and proteins in the ubiquitin-proteasome pathway. Three proteins were uniquely altered in vaginal carcinoma (DDX48, erbB3-binding protein and biliverdin reductase) and five in cervical carcinoma (peroxiredoxin 2, annexin A2, sarcomeric tropomyosin kappa, human ribonuclease inhibitor and prolyl-4-hydrolase beta). The identified proteins imply involvement of multiple different cellular pathways in the carcinogenesis of vaginal carcinoma. Similar protein alterations were found between vaginal and cervical carcinoma suggesting common tumourigenesis. However, the expression level of some of these proteins markedly differs among the three tissue specimens indicating that they might be useful molecular markers.
目的是鉴定阴道癌中差异表达的蛋白质,以阐明相关的癌症相关蛋白质。使用二维凝胶电泳(2-DE)和基质辅助激光解吸电离飞行时间质谱(MALDI-TOF)对总共16份新鲜冷冻组织活检样本进行分析,其中包括5份正常阴道上皮活检样本、6份原发性阴道癌活检样本和5份原发性宫颈癌活检样本。在非肿瘤组织和肿瘤组织之间鉴定出的43种蛋白质表达有显著变化,其中26种上调,17种下调。一些蛋白质在阴道癌和宫颈癌中的变化相似,包括细胞骨架蛋白、肿瘤抑制蛋白、与凋亡相关的癌蛋白以及泛素-蛋白酶体途径中的蛋白质。三种蛋白质在阴道癌中独特地发生改变(DDX48、erbB3结合蛋白和胆绿素还原酶),五种在宫颈癌中独特地发生改变(过氧化物还原酶2、膜联蛋白A2、肌节原肌球蛋白κ、人核糖核酸酶抑制剂和脯氨酰-4-羟化酶β)。鉴定出的蛋白质表明多种不同的细胞途径参与了阴道癌的致癌过程。在阴道癌和宫颈癌之间发现了相似的蛋白质改变,提示存在共同的肿瘤发生机制。然而,这些蛋白质中的一些在三种组织样本中的表达水平明显不同,表明它们可能是有用的分子标志物。