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Molecules 2011, 16(4), 3048-3065; doi:10.3390/molecules16043048

2D-DIGE Proteomic Analysis of Changes in Estrogen/Progesterone-Induced Rat Breast Hyperplasia upon Treatment with the Mongolian Remedy RuXian-I

1, 2, 2, 2, 2,*  and 1,*
1 Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China 2 Affiliated Hospital of Inner Mongolia University for the Nationalities, Institute of Mongolia and Western Medicinal treatment, Tongliao 028000, China
* Authors to whom correspondence should be addressed.
Received: 26 January 2011 / Revised: 31 March 2011 / Accepted: 2 April 2011 / Published: 8 April 2011
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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 a 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.
Keywords: 2D-DIGE; estrogen; proteomics; breast hyperplasia; Mongolian medicine; rat 2D-DIGE; estrogen; proteomics; breast hyperplasia; Mongolian medicine; rat
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

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Wang, Z.-C.; E, D.; Batu, D.-L.; Saixi, Y.-L.; Zhang, B.; Ren, L.-Q. 2D-DIGE Proteomic Analysis of Changes in Estrogen/Progesterone-Induced Rat Breast Hyperplasia upon Treatment with the Mongolian Remedy RuXian-I. Molecules 2011, 16, 3048-3065.

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