Varnum Susan M, Covington Chandice C, Woodbury Ronald L, Petritis Konstantinos, Kangas Lars J, Abdullah Mohamed S, Pounds Joel G, Smith Richard D, Zangar Richard C
Pacific Northwest National Laboratory, Richland, WA 99352, USA.
Breast Cancer Res Treat. 2003 Jul;80(1):87-97. doi: 10.1023/A:1024479106887.
Mammary ductal cells are the origin for 70-80% of breast cancers. Nipple aspirate fluid (NAF) contains proteins directly secreted by the ductal and lobular epithelium in non-lactating women. Proteomic approaches offer a largely unbiased way to evaluate NAF as a source of biomarkers and are sufficiently sensitive for analysis of small NAF volumes (10-50 microl). In this study, we initially evaluated a new process for obtaining NAF and discovered that this process resulted in a volume of NAF that was suitable for analysis in approximately 90% of subjects. Proteomic characterization of NAF identified 64 proteins. Although this list primarily includes abundant and moderately abundant NAF proteins, very few of these proteins have previously been reported in NAF. At least 15 of the NAF proteins identified have previously been reported to be altered in serum or tumor tissue from women with breast cancer, including cathepsin D and osteopontin. In summary, this study provides the first characterization of the NAF proteome and identifies several candidate proteins for future studies on breast cancer markers in NAF.
乳腺导管细胞是70 - 80%乳腺癌的起源。乳头抽吸液(NAF)包含非哺乳期女性导管和小叶上皮直接分泌的蛋白质。蛋白质组学方法为评估NAF作为生物标志物来源提供了一种基本无偏差的方式,并且对少量NAF样本(10 - 50微升)的分析具有足够的敏感性。在本研究中,我们首先评估了一种获取NAF的新方法,发现该方法能使约90%的受试者获得适合分析的NAF量。对NAF的蛋白质组学表征鉴定出64种蛋白质。尽管该列表主要包括丰度较高和中等丰度的NAF蛋白质,但这些蛋白质中很少有此前在NAF中被报道过。已鉴定出的NAF蛋白质中至少有15种此前报道在乳腺癌女性的血清或肿瘤组织中发生了改变,包括组织蛋白酶D和骨桥蛋白。总之,本研究首次对NAF蛋白质组进行了表征,并鉴定出几种候选蛋白质,用于未来关于NAF中乳腺癌标志物的研究。