Role of the ERas gene in gastric cancer cells

Liu,Yang; Wang,Zhaoqian; Li,Huiming; Wu,Zhaoping; Wei,Fang; Wang,Huiping

doi:10.3892/or.2013.2417

Role of the ERas gene in gastric cancer cells

Authors:
- Yang Liu
- Zhaoqian Wang
- Huiming Li
- Zhaoping Wu
- Fang Wei
- Huiping Wang
View Affiliations

Affiliations: Experimental Research Center, First People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200080, P.R. China, Shanghai Gezhi High School, Shanghai 200001, P.R. China
Published online on: April 23, 2013 https://doi.org/10.3892/or.2013.2417
Pages: 50-56
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License [CC BY_NC 3.0].

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

As a novel member of the Ras family, ERas, found in murine embryonic stem (ES) cells in 2003, was considered a pseudogene. To date, there are a few reports on the relationship between ERas and tumors. It was recently suggested that ERas could affect gastric carcinoma (GC) metastasis, but no significant relationship was found with tumor proliferation. Since ERas plays an important role in tumor-like growth of ES cells subcutaneously injected into nude mice, we hypothesized that ERas plays a role in tumor proliferation. In this experiment, we selected 7 GC strains from different sources with different differentiation degrees, we detected the expression of full length ERas transcript, and selected two ERas highly expressing GC strains, MKN‑28 and BGC‑823. After knocking down the ERas gene by siRNA, we observed that there was a significant decrease in proliferation, metastasis as well as clonality. Therefore, ERas is confirmed to be an important gene in affecting tumor proliferation and metastasis. Furthermore, the significance of the ERas mechanism and signaling pathway is shown.

View Figures

View References

1	Takahashi K, Mitsui K and Yamanaka S: Role of ERas in promoting tumour-like properties in mouse embryonic stem cells. Nature. 423:541–545. 2003. View Article : Google Scholar : PubMed/NCBI
2	Kameda T and Thomson JA: Human ERas gene has an upstream premature polyadenylation signal that results in a truncated, noncoding transcript. Stem Cells. 23:1535–1540. 2005. View Article : Google Scholar
3	Takahashi K, Murakami M and Yamanaka S: Role of the phosphoinositide 3-kinase pathway in mouse embryonic stem (ES) cells. Biochem Soc Trans. 33:1522–1525. 2005. View Article : Google Scholar : PubMed/NCBI
4	Takahashi K, Nakagawa M, Young SG and Yamanaka S: Differential membrane localization of ERas and Rheb, two Ras-related proteins involved in the phosphatidylinositol 3-kinase/mTOR pathway. J Biol Chem. 280:32768–32774. 2005. View Article : Google Scholar : PubMed/NCBI
5	Fasano O, Aldrich T, Tamanoi F, et al: Analysis of the transforming potential of the human H-ras gene by random mutagenesis. Proc Natl Acad Sci USA. 81:4008–4012. 1984. View Article : Google Scholar : PubMed/NCBI
6	Schubbert S, Shannon K and Bollag G: Hyperactive Ras in developmental disorders and cancer. Nat Rev Cancer. 7:295–308. 2007. View Article : Google Scholar : PubMed/NCBI
7	Seeburg PH, Colby WW, Capon DJ, et al: Biological properties of human c-Ha-ras1 genes mutated at codon 12. Nature. 312:71–75. 1984. View Article : Google Scholar : PubMed/NCBI
8	Cass LA and Meinkoth JL: Ras signaling through PI3K confers hormone-independent proliferation that is compatible with differentiation. Oncogene. 19:924–932. 2000. View Article : Google Scholar : PubMed/NCBI
9	Deora AA, Hajjar DP and Lander HM: Recruitment and activation of Raf-1 kinase by nitric oxide-activated Ras. Biochemistry. 39:9901–9908. 2000. View Article : Google Scholar : PubMed/NCBI
10	Rodriguez-Viciana P, Warne PH, Dhand R, et al: Phosphatidylinositol-3-OH kinase as a direct target of Ras. Nature. 370:527–532. 1994. View Article : Google Scholar : PubMed/NCBI
11	Moodie SA, Willumsen BM, Weber MJ and Wolfman A: Complexes of Ras.GTP with Raf-1 and mitogen-activated protein kinase kinase. Science. 260:1658–1661. 1993. View Article : Google Scholar : PubMed/NCBI
12	Zhang XF, Settleman J, Kyriakis JM, et al: Normal and oncogenic p21ras proteins bind to the amino-terminal regulatory domain of c-Raf-1. Nature. 364:308–313. 1993. View Article : Google Scholar : PubMed/NCBI
13	Chang EH, Gonda MA, Ellis RW, et al: Human genome contains four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses. Proc Natl Acad Sci USA. 79:4848–4852. 1982. View Article : Google Scholar
14	Miyoshi J, Kagimoto M, Soeda E and Sakaki Y: The human c-Ha-ras2 is a processed pseudogene inactivated by numerous base substitutions. Nucleic Acids Res. 12:1821–1828. 1984. View Article : Google Scholar : PubMed/NCBI
15	Yasuda K, Yashiro M, Sawada T, et al: ERas oncogene expression and epigenetic regulation by histone acetylation in human cancer cells. Anticancer Res. 27:4071–4075. 2007.PubMed/NCBI
16	Yashiro M, Yasuda K, Nishii T, et al: Epigenetic regulation of the embryonic oncogene ERas in gastric cancer cells. Int J Oncol. 35:997–1003. 2009. View Article : Google Scholar : PubMed/NCBI
17	Kaizaki R, Yashiro M, Shinto O, et al: Expression of ERas oncogene in gastric carcinoma. Anticancer Res. 29:2189–2193. 2009.PubMed/NCBI
18	Kubota E, Kataoka H, Tanaka M, et al: ERas enhances resistance to CPT-11 in gastric cancer. Anticancer Res. 31:3353–3360. 2011.PubMed/NCBI
19	Bjorklund LM, Sánchez-Pernaute R, Chung S, et al: Embryonic stem cells develop into functional dopaminergic neurons after transplantation in a Parkinson rat model. Proc Natl Acad Sci USA. 99:2344–2349. 2002. View Article : Google Scholar : PubMed/NCBI
20	Kubota E, Kataoka H, Aoyama M, et al: Role of ES cell-expressed Ras (ERas) in tumorigenicity of gastric cancer. Am J Pathol. 177:955–963. 2010. View Article : Google Scholar : PubMed/NCBI
21	Rao M: Conserved and divergent paths that regulate self-renewal in mouse and human embryonic stem cells. Dev Biol. 275:269–286. 2004. View Article : Google Scholar : PubMed/NCBI
22	Hsu RJ, Ho JY, Cha TL, et al: WNT10A plays an oncogenic role in renal cell carcinoma by activating WNT/β-catenin pathway. PLoS One. 7:e476492012.PubMed/NCBI
23	Li WG, Yuan YZ, Qiao MM and Zhang YP: High dose glargine alters the expression profiles of microRNAs in pancreatic cancer cells. World J Gastroenterol. 18:2630–2639. 2012. View Article : Google Scholar : PubMed/NCBI