Programme of Molecular Biology and Bioinformatics, Department of Anatomy, Faculty of Science, Prince of Songkla University, Hat Yai, Songkhla 90110, Thailand.
Oncol Rep. 2011 Jul;26(1):185-91. doi: 10.3892/or.2011.1266. Epub 2011 Apr 15.
Axillary lymph node (ALN) metastasis is a key step of tumor progression in breast cancer and is associated with an unfavorable prognosis. However, the mechanisms of this process are not well understood. Proteomic technologies have led to identification of specific protein markers and a better understanding of the cellular processes. To explore this, differential protein expression was analyzed between node-positive breast carcinoma and node-negative breast carcinoma (11 samples) and between primary breast carcinoma and matched metastatic ALN (five pairs) using a combination of 2D-SDS-PAGE and LC-MC/MS. Of the total 678 protein spots, 19 proteins were up-regulated and 3 proteins were down-regulated in node-positive breast carcinomas compared to node-negative breast carcinomas. Four up-regulated proteins were identified, namely annexin 5, carbonic anhydrase I, peroxiredoxin 6 and proteasome α2 subunit. For proteins altered in metastatic ALN compared to primary tumors, 6 of 14 up-regulated proteins were identified: heat shock 70 kDa protein 5, protein disulfide isomerase, prolyl 4-hydroxylase β subunit precursor, lactate dehydrogenase B, triosephosphate isomerase 1 and β-tubulin and 5 of 23 down-regulated proteins were identified including 90 kDa heat shock protein, chain A apo-human serum transferrin, chain A α1-antitrypsin, enolase 1 and macrophage migration inhibitory factor. Immunohistochemistry showed stronger immunostaining for β-tubulin in metastatic ALN compared to primary breast tumor. All of the identified proteins function in various processes involved in cell survival and growth. Our results suggest that these processes are critical for tumor progression and metastasis and the proteins identified could be candidate markers of clinical usefulness.
腋窝淋巴结（ALN）转移是乳腺癌肿瘤进展的关键步骤，与预后不良相关。然而，这一过程的机制尚不清楚。蛋白质组学技术已经确定了特定的蛋白质标记物，并更好地了解了细胞过程。为了探索这一点，使用二维 SDS-PAGE 和 LC-MC/MS 组合，分析了淋巴结阳性乳腺癌与淋巴结阴性乳腺癌（11 个样本）之间以及原发性乳腺癌与匹配转移性 ALN（5 对）之间的差异蛋白质表达。在总共 678 个蛋白质斑点中，与淋巴结阴性乳腺癌相比，淋巴结阳性乳腺癌中有 19 个蛋白质上调，3 个蛋白质下调。鉴定出 4 种上调的蛋白质，即膜联蛋白 5、碳酸酐酶 I、过氧化物酶 6 和蛋白酶体 α2 亚基。与原发性肿瘤相比，在转移性 ALN 中改变的蛋白质中，鉴定出 14 个上调蛋白中的 6 个：热休克 70 kDa 蛋白 5、蛋白二硫键异构酶、脯氨酰 4-羟化酶 β 亚基前体、乳酸脱氢酶 B、磷酸丙糖异构酶 1 和β-微管蛋白，23 个下调蛋白中有 5 个：90 kDa 热休克蛋白、人血清转铁蛋白 A 链、A1 抗胰蛋白酶 A 链、烯醇酶 1 和巨噬细胞移动抑制因子。免疫组织化学显示转移性 ALN 中β-微管蛋白的免疫染色强度强于原发性乳腺癌。所有鉴定出的蛋白质在参与细胞存活和生长的各种过程中发挥作用。我们的结果表明，这些过程对于肿瘤进展和转移至关重要，并且鉴定出的蛋白质可能是具有临床用途的候选标志物。
