Negative association of R-Ras activation and breast cancer development

Song,Jie; Zheng,Bin; Bu,Xiaobo; Fei,Yaoyuan; Shi,Shuliang

doi:10.3892/or.2014.3121

Negative association of R-Ras activation and breast cancer development

Authors:
- Jie Song
- Bin Zheng
- Xiaobo Bu
- Yaoyuan Fei
- Shuliang Shi
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Affiliations: Key Laboratory of Cancer Prevention and Treatment of Heilongjiang Province and Department of Biology, Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China, Center for Bioengineering and School of Electrical and Computer Engineering, University of Oklahoma, Norman, OK 73019, USA, School of Life Science and Technology, Harbin Institute of Technology, Harbin, Heilongjiang 150001, P.R. China
Published online on: April 2, 2014 https://doi.org/10.3892/or.2014.3121
Pages: 2776-2784

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Abstract

R-Ras, a member of the Ras superfamily, is expressed in a wide variety of tissues and regulates cell adhesion, migration, differentiation and apoptosis. Research has raised the possibility that R-Ras may function as a positive regulator of cell proliferation and transformation in the breast. To understand the possible role of R-Ras in breast epithelial carcinogenesis, the expression and activation of R-Ras were detected in each of 69 pairs of breast cancer tissues and normal tumor-adjacent tissue samples by qRT-PCR, western blot analysis and GST pull down assay; 12 available cell lines were also subjected to western blot analysis and GST pull down assay. To further address the role of R-Ras in transformation-related phenotype formation of breast cancer cell line MCF-7 in vitro, R-Ras38V, a constitutively activated mutant of R-Ras, was transfected into MCF-7 cells, and the cell proliferation, migration and cell cycle distribution were analyzed. The results showed that although there was slight difference in the protein expression of R-Ras between the breast cancer tissues and normal tissues, the activation of R-Ras was reduced in 63.8% of the cancer tissues when compared to the normal tissue samples. In addition, the results also showed that R-Ras38V inhibited cell proliferation, migration and cell cycle progression in the presence of serum. Contradicting the positive association reported in previous studies, our results indicate that R-Ras activation may negatively regulate the transformation of breast epithelial cells, and the loss of activation of R-Ras may be involved in the carcinogenesis of breast cancer. To solve this controversy, further independent studies are needed to validate our study results.

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