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2D-DIGE Proteomic Analysis of Changes in Estrogen/Progesterone-Induced Rat Breast Hyperplasia upon Treatment with the Mongolian Remedy RuXian-I
Department of Experimental Pharmacology and Toxicology, School of Pharmaceutical Sciences, Jilin University, Changchun 130021, China
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; in revised form: 31 March 2011 / Accepted: 2 April 2011 / Published: 8 April 2011
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 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
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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.
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(4):3048-3065.
Wang, Zhong-Chao; E, Du; Batu, De-Ligen; Saixi, Ya-Latu; Zhang, Bin; Ren, Li-Qun. 2011. "2D-DIGE Proteomic Analysis of Changes in Estrogen/Progesterone-Induced Rat Breast Hyperplasia upon Treatment with the Mongolian Remedy RuXian-I." Molecules 16, no. 4: 3048-3065.