2D-DIGE proteomic analysis of changes in estrogen/progesterone-induced rat breast hyperplasia upon treatment with the Mongolian remedy RuXian-I.
2D-DIGE proteomic analysis of changes in estrogen/progesterone-induced rat breast hyperplasia upon treatment with the Mongolian remedy RuXian-I.
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DOI：
10.3390/molecules16043048
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发表时间：
2011-04-08
期刊：
影响因子：
--
通讯作者：
Ren LQ
中科院分区：
文献类型：
--
作者：
Wang ZC;E D;Batu DL;Saixi YL;Zhang B;Ren LQ
在中国内蒙古自治区，乳仙I号传统上被用作治疗乳腺增生的药物。作为研究与乳腺I号治疗相关的生物标志物的第一步，对大鼠乳腺组织进行了全蛋白质组分析。首先，通过注射雌二醇和孕酮诱导大鼠乳腺增生。用乳仙Ⅰ号治疗后，增生明显减少，表现为乳头直径减小和乳房病理改变。随后，我们使用基于尺寸的2D-DIGE，MALDI-TOF/TOF-MS和生物信息学相结合的方法来分析对照组，模型组和乳仙-I治疗组的数据。使用这种方法，鉴定了17种受影响的蛋白质。其中15种蛋白（包括annexin A1、annexin A2、superoxide dismutase [Mn]、peroxiredoxin-1、肿瘤抑制蛋白和α B-晶状体蛋白）在模型组表达明显上调，在乳纤Ⅰ号治疗后表达下调，而2种蛋白（TGFAP蛋白和myosin-4）表达变化趋势相反。免疫组化证实膜联蛋白A1的表达。超氧化物歧化酶（SOD）活性的表达被生化证实。这些结果表明，乳腺I号通过调节细胞周期、免疫系统、代谢、信号传导等来治疗大鼠乳腺增生。这些蛋白质（膜联蛋白A1、超氧化物歧化酶[Mn]、α B-晶体蛋白和翻译控制的肿瘤蛋白等）的差异表达与乳腺癌的发生和转移有关。这些结果不仅为深入研究乳腺Ⅰ号的作用机制提供了有价值的信息，而且对乳腺增生和乳腺癌的诊断和预后也有一定的指导意义。
RuXian-I has traditionally been used as a remedy for breast hyperplasia in the Inner Mongolia Autonomous Region of China. As a first step toward the investigation of biomarkers associated with RuXian-I treatment, a proteome-wide analysis of rat breast tissue was conducted. First, rat breast hyperplasia was induced by injection of estradiol and progesterone. After treatment with RuXian-I, there is a marked decrease in the hyperplasia, as can be shown by decreases in the nipple diameter and the pathological changes in breast. Subsequently, we used an approach that integrates size-based 2D-DIGE, MALDI-TOF/TOF-MS, and bioinformatics to analyze data from the control group, the model group and the RuXian-I treatment group. Using this approach, seventeen affected proteins were identified. Among these, 15 (including annexin A1, annexin A2, superoxide dismutase [Mn], peroxiredoxin-1, translationally-controlled tumor protein and α B-crystallin) were significantly up-regulated in the model group and down-regulated upon treatment with RuXian-I, and two (Tpil protein and myosin-4) have the opposite change trend. The expression of annexin A1 was confirmed using immunohistochemistry. The expression of superoxide dismutase (SOD) activity was confirmed biochemically. These results indicated that RuXian-I treats rat breast hyperplasia through regulation of cell cycle, immune system, metabolic, signal transduction, etc. The differential expressions of these proteins (annexin A1, superoxide dismutase [Mn], alpha B-crystallins and translationally controlled tumor protein, among others) were associated with occurrence and metastasis of breast cancer. These findings might provide not only far-reaching valuable insights into the mechanism of RuXian-I action, but also leads for prognosis and diagnosis of breast hyperplasia and breast cancer.
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