Abstract
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.
Highlights
Much research has been devoted to malignant lesions of the breast because breast cancer is the most common malignancy in women in Western countries; benign lesions of the breast are far more frequent than malignant ones
The control group had the following phenotypes in various regions: in the duct, there was a lack of ectasia and of significant proliferation of epithelial cells, and an epithelial arrangement; the lobules were very small with 1–3 acini per lobule and no expansion into the acinar cavity; and there were no significant stromal hyperplasia
Several of the differentially expressed proteins identified in this study, e.g., annexin A1, Glutathione S-transferase P1 (GST P1) and α B-crystallin, are related to mitogen-activated protein kinases (MAPK) pathways, and others are related to breast cancer occurrence and metastasis
Summary
Much research has been devoted to malignant lesions of the breast because breast cancer is the most common malignancy in women in Western countries; benign lesions of the breast are far more frequent than malignant ones. Multiple applied estrogen or estrogen receptor antagonist agents, including tamoxifen, have been used These drugs can relieve symptoms in patients, they have many side effects and complications, and their use can lead to endocrine disorders [1]. There have been several reports comparing the expression profiles of proteins in breast cancer tissues with those in nontumor breast tissues [4,5,6]. Expression profiles of proteins in breast hyperplasia have not been reported. In order to gain a better insight into the mechanism of RuXian-I’s efficacy, diagnosis, therapy, outcomes, and prognosis in breast hyperplasia, and the relation between breast hyperplasia and breast cancer, we used intramuscular estrogen and progesterone injections to induce rat breast hyperplasia and 2D-DIGE to study the proteins associated with RuXian-I treatment. MALDI-TOF/TOF-MS, and changes in the expression of the proteins of interest were further validated using immunohistochemical and biochemical detection methods
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