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Article

Negative association of R-Ras activation and breast cancer development

  • Authors:
    • Jie Song
    • Bin Zheng
    • Xiaobo Bu
    • Yaoyuan Fei
    • Shuliang Shi
  • View Affiliations / Copyright

    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
  • Pages: 2776-2784
    |
    Published online on: April 2, 2014
       https://doi.org/10.3892/or.2014.3121
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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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1 

Webb CP, Van Aelst L, Wigler MH and Vande Woude GF: Signaling pathways in Ras-mediated tumorigenicity and metastasis. Proc Natl Acad Sci USA. 95:8773–8778. 1998. View Article : Google Scholar : PubMed/NCBI

2 

Lowe DG, Capon DJ, Delwart E, et al: Structure of the human and murine R-ras genes, novel genes closely related to ras proto-oncogenes. Cell. 48:137–146. 1987.PubMed/NCBI

3 

Tada M, Kobayashi T, Kontani K and Katada T: Recent progress in the research on small GTP-binding protein. Nihon Yakurigaku Zasshi. 130:373–379. 2007.(In Japanese).

4 

Hall A: The cellular functions of small GTP-binding proteins. Science. 249:635–640. 1990. View Article : Google Scholar : PubMed/NCBI

5 

Bourne HR, Sanders DA and Mccormick F: The GTPase superfamily: a conserved switch for diverse cell functions. Nature. 348:125–132. 1990. View Article : Google Scholar : PubMed/NCBI

6 

Self AJ, Caron E, Paterson HF and Hall A: Analysis of R-Ras signaling pathways. J Cell Sci. 114:1357–1366. 2001.PubMed/NCBI

7 

Oertli B, Han J, Marte BM, et al: The effector loop and prenylation site of R-Ras are involved in the regulation of integrin function. Oncogene. 19:4961–4969. 2000. View Article : Google Scholar : PubMed/NCBI

8 

Fernandez-Sarabia MJ and Bischoff JR: Bcl-2 associates with the ras related protein R-ras p23. Nature. 366:274–285. 1993. View Article : Google Scholar : PubMed/NCBI

9 

Wang HG, Millan JA, Cox AD, et al: R-Ras promotes apoptosis caused by growth factor deprivation via a Bcl-2 suppressible mechanism. J Cell Biol. 129:1103–1114. 1995. View Article : Google Scholar : PubMed/NCBI

10 

Hughes PE, Oertli B, Han J, et al: R-Ras regulation of integrin function. Methods Enzymol. 333:163–171. 2001. View Article : Google Scholar : PubMed/NCBI

11 

Kinashi T, Katagiri K, Watanabe S, et al: Distinct mechanisms of α5β1 integrin activation by Ha-Ras and R-Ras. J Biol Chem. 275:22590–22596. 2000.

12 

Kwong L, Wozniak MA, Collins AS, et al: R-Ras promotes focal adhesion formation through focal adhesion kinase and p130Cas by a novel mechanism that differs from integrins. Mol Cell Biol. 23:933–949. 2003. View Article : Google Scholar : PubMed/NCBI

13 

Wang B, Zou JX, Ek-Rylander B, et al: R-Ras contains a proline-rich site that binds to SH3 domains and is required for integrin activation by R-Ras. J Biol Chem. 275:5222–5227. 2000. View Article : Google Scholar : PubMed/NCBI

14 

Furuhjelm J and Peränen J: The C-terminal end of R-Ras contains a focal adhesion targeting signal. J Cell Sci. 116:3729–3738. 2003. View Article : Google Scholar : PubMed/NCBI

15 

Oinuma I, Ito Y, Katoh H and Negishi M: Semaphorin 4D/Plexin-B1 stimulates PTEN activity through R-RasGTPase-activating protein activity, inducing growth cone collapse in hippocampal neurons. J Biol Chem. 285:28200–28209. 2010. View Article : Google Scholar : PubMed/NCBI

16 

Komatsu M and Ruoslahti E: R-Ras is a global regulator of vascular regeneration that suppresses intimal hyperplasia and tumor angiogenesis. Nat Med. 11:1346–1350. 2005. View Article : Google Scholar : PubMed/NCBI

17 

Inuzuka T, Tsuda M, Kawaguchi H, et al: Transcription factor 8 activates R-Ras to regulate angiogenesis. Biochem Biophys Res Commun. 379:510–523. 2009. View Article : Google Scholar : PubMed/NCBI

18 

Sawada J and Komatsu M: Normalization of tumor vasculature by R-Ras. Cell Cycle. 11:4285–4296. 2012. View Article : Google Scholar : PubMed/NCBI

19 

Sawada J, Urakami T, Li F, et al: Small GTPase R-Ras regulates integrity and functionality of tumor blood vessels. Cancer Cell. 22:235–249. 2012. View Article : Google Scholar : PubMed/NCBI

20 

Xu L and Komatsu M: Promoter cloning and characterization of the anti-vascular proliferation gene, R-ras: role of Ets- and Sp-binding motifs. J Biol Chem. 284:2706–2718. 2009. View Article : Google Scholar : PubMed/NCBI

21 

Erdogan M, Pozzi A, Bhowmick N, et al: Transforming growth factor-β (TGF-β) and TGF-β-associated kinase 1 are required for R-Ras-mediated transformation of mammary epithelial cells. Cancer Res. 68:6224–6231. 2008.

22 

Keely PJ, Rusyn EV, Cox AD and Parise LV: R-Ras signals through specific integrin α cytoplasmic domains to promote migration and invasion of breast epithelial cells. J Cell Biol. 145:1077–1088. 1999.

23 

Yu Y and Feig LA: Involvement of R-Ras and RalGTPases in estrogen-independent proliferation of breast cancer cells. Oncogene. 21:7557–7568. 2002. View Article : Google Scholar : PubMed/NCBI

24 

Yu Y, Hao Y and Feig LA: The R-RasGTPase mediates cross talk between estrogen and insulin signaling in breast cancer cells. Mol Cell Biol. 26:6372–6380. 2006. View Article : Google Scholar : PubMed/NCBI

25 

Ross JS, Linette GP, Stec J, et al: Breast cancer biomarkers and molecular medicine. Expert Rev Mol Diagn. 3:573–585. 2003. View Article : Google Scholar

26 

Valencla A, Chardin P, Wittinghofer A, et al: The ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry. 30:4637–4648. 1991. View Article : Google Scholar : PubMed/NCBI

27 

Cox AD, Brtva TR, Lowe DG, et al: R-Ras induces malignant, but not morphologic, transformation of NIH3T3 cells. Oncogene. 9:3281–3288. 1994.PubMed/NCBI

28 

Wozniak MA, Kwong L, Chodniewicz D, et al: R-Ras controls membrane protrusion and cell migration through the spatial regulation of Rac and Rho. Mol Biol Cell. 16:84–96. 2005. View Article : Google Scholar : PubMed/NCBI

29 

Nakada M, Niska JA, Tran NL, et al: EphB2/R-Ras signaling regulates glioma cell adhesion, growth, and invasion. Am J Pathol. 167:565–576. 2005. View Article : Google Scholar : PubMed/NCBI

30 

Rincón-Arano H, Rosales R, Mora N, et al: R-Ras promotes tumor growth of cervical epithelial cells. Cancer. 97:575–585. 2003.PubMed/NCBI

31 

Mora N, Rosales R and Rosales C: R-Ras promotes metastasis of cervical cancer epithelial cells. Cancer Immunol Immunother. 56:535–544. 2007. View Article : Google Scholar : PubMed/NCBI

32 

Wang J, Yao M, Gu J, et al: Blocking HSF1 by dominant- negative mutant to sensitize tumor cell to hyperthermia. Biochem Biophys Res Commun. 290:1454–1461. 2002. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Song J, Zheng B, Bu X, Fei Y and Shi S: Negative association of R-Ras activation and breast cancer development. Oncol Rep 31: 2776-2784, 2014.
APA
Song, J., Zheng, B., Bu, X., Fei, Y., & Shi, S. (2014). Negative association of R-Ras activation and breast cancer development. Oncology Reports, 31, 2776-2784. https://doi.org/10.3892/or.2014.3121
MLA
Song, J., Zheng, B., Bu, X., Fei, Y., Shi, S."Negative association of R-Ras activation and breast cancer development". Oncology Reports 31.6 (2014): 2776-2784.
Chicago
Song, J., Zheng, B., Bu, X., Fei, Y., Shi, S."Negative association of R-Ras activation and breast cancer development". Oncology Reports 31, no. 6 (2014): 2776-2784. https://doi.org/10.3892/or.2014.3121
Copy and paste a formatted citation
x
Spandidos Publications style
Song J, Zheng B, Bu X, Fei Y and Shi S: Negative association of R-Ras activation and breast cancer development. Oncol Rep 31: 2776-2784, 2014.
APA
Song, J., Zheng, B., Bu, X., Fei, Y., & Shi, S. (2014). Negative association of R-Ras activation and breast cancer development. Oncology Reports, 31, 2776-2784. https://doi.org/10.3892/or.2014.3121
MLA
Song, J., Zheng, B., Bu, X., Fei, Y., Shi, S."Negative association of R-Ras activation and breast cancer development". Oncology Reports 31.6 (2014): 2776-2784.
Chicago
Song, J., Zheng, B., Bu, X., Fei, Y., Shi, S."Negative association of R-Ras activation and breast cancer development". Oncology Reports 31, no. 6 (2014): 2776-2784. https://doi.org/10.3892/or.2014.3121
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