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Article

RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways

  • Authors:
    • Yingdong Xu
    • Na Deng
    • Xiaoou Wang
    • Yinghui Chen
    • Guiji Li
    • Hua Fan
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The First Affiliated Hospital of China Medical University, Shenyang, Liaoning 110001, P.R. China, Department of Oncology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China, Department of Hematology, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, P.R. China
  • Pages: 965-970
    |
    Published online on: May 17, 2017
       https://doi.org/10.3892/ol.2017.6182
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Abstract

Raf kinase trapping to Golgi (RKTG) is reported to be a tumor suppressor in a number of solid tumors due to its negative modulation of the Ras/Raf/mitogen‑activated protein kinase kinase/extracellular signal‑regulated kinase (ERK) pathways. However, the role of RKTG in the progression of leukemia remains unknown. In the present study, a human leukemia U937 cell line overexpressing RKTG was established, and the effect of RKTG on proliferation, cell cycle and apoptosis of human leukemia cells was analyzed. The results of the present study demonstrated that exogenous overexpression of RKTG significantly inhibited cell proliferation, which was accompanied by cell cycle arrest. Apoptosis assay and Hoechst staining demonstrated that the percentage of apoptotic cells in RKTG overexpressing cells was markedly increased. Furthermore, western blotting showed that RKTG overexpression significantly increased the level of cleaved caspase 3, B‑cell lymphoma 2 (Bcl2)‑associated X apoptosis regulator and reduced the level of Bcl‑2. In addition, the activation of ERK and phosphoinositide 3‑kinase (PI3K)/AKT serine/threonine kinase 1 signaling pathways in human leukemia cells was also suppressed by RKTG overexpression. In conclusion, the present study demonstrated the tumor‑suppressive effect of RKTG on human leukemia cells, which seem to be partially dependent on the suppression of ERK and PI3K/AKT signaling. Overexpression of RKTG may be a potential therapeutic target for the treatment of leukemia.
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1 

Estey E and Döhner H: Acute myeloid leukaemia. Lancet. 368:1894–1907. 2006. View Article : Google Scholar : PubMed/NCBI

2 

Smith M, Barnett M, Bassan R, Gatta G, Tondini C and Kern W: Adult acute myeloid leukaemia. Crit Rev Oncol Hematol. 50:197–222. 2004. View Article : Google Scholar : PubMed/NCBI

3 

Lowenberg B, Downing JR and Burnett A: Acute myeloid leukemia. N Engl J Med. 341:1051–1062. 1999. View Article : Google Scholar : PubMed/NCBI

4 

Jemal A, Siegel R, Xu J and Ward E: Cancer statistics, 2010. CA Cancer J Clin. 60:277–300. 2010. View Article : Google Scholar : PubMed/NCBI

5 

Tallman MS, Gilliland DG and Rowe JM: Drug therapy for acute myeloid leukemia. Blood. 106:1154–1163. 2005. View Article : Google Scholar : PubMed/NCBI

6 

Ferrara F: Unanswered questions in acute myeloid leukaemia. Lancet Oncol. 5:443–450. 2004. View Article : Google Scholar : PubMed/NCBI

7 

Look AT: Oncogenic transcription factors in the human acute leukemias. Science. 278:1059–1064. 1997. View Article : Google Scholar : PubMed/NCBI

8 

Castilla LH, Garrett L, Adya N, Orlic D, Dutra A, Anderson S, Owens J, Eckhaus M, Bodine D and Liu PP: The fusion gene Cbfb-MYH11 blocks myeloid differentiation and predisposes mice to acute myelomonocytic leukaemia. Nat Genet. 23:144–146. 1999. View Article : Google Scholar : PubMed/NCBI

9 

Falini B, Nicoletti I, Martelli MF and Mecucci C: Acute myeloid leukemia carrying cytoplasmic/mutated nucleophosmin (NPMc+ AML): Biologic and clinical features. Blood. 109:874–885. 2007. View Article : Google Scholar : PubMed/NCBI

10 

Christiansen DH, Andersen MK, Desta F and Pedersen-Bjergaard J: Mutations of genes in the receptor tyrosine kinase (RTK)/RAS-BRAF signal transduction pathway in therapy-related myelodysplasia and acute myeloid leukemia. Leukemia. 19:2232–2240. 2005. View Article : Google Scholar : PubMed/NCBI

11 

Feng L, Xie X, Ding Q, Luo X, He J, Fan F, Liu W, Wang Z and Chen Y: Spatial regulation of Raf kinase signaling by RKTG. Proc Natl Acad Sci USA. 104:pp. 14348–14353. 2007; View Article : Google Scholar : PubMed/NCBI

12 

Fan F, Feng L, He J, Wang X, Jiang X, Zhang Y, Wang Z and Chen Y: RKTG sequesters B-Raf to the Golgi apparatus and inhibits the proliferation and tumorigenicity of human malignant melanoma cells. Carcinogenesis. 29:1157–1163. 2008. View Article : Google Scholar : PubMed/NCBI

13 

Cano E and Mahadevan LC: Parallel signal processing among mammalian MAPKs. Trends Biochem Sci. 20:117–122. 1995. View Article : Google Scholar : PubMed/NCBI

14 

Zhang Y, Jiang X, Qin X, Ye D, Yi Z, Liu M, Bai O, Liu W, Xie X, Wang Z, et al: RKTG inhibits angiogenesis by suppressing MAPK-mediated autocrine VEGF signaling and is downregulated in clear-cell renal cell carcinoma. Oncogene. 29:5404–5415. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Wang X, Li X, Fan F, Jiao S, Wang L, Zhu L, Pan Y, Wu G, Ling ZQ, Fang J and Chen Y: PAQR3 plays a suppressive role in the tumorigenesis of colorectal cancers. Carcinogenesis. 33:2228–2235. 2012. View Article : Google Scholar : PubMed/NCBI

16 

Wu Q, Zhuang K and Li H: PAQR3 plays a suppressive role in laryngeal squamous cell carcinoma. Tumour Biol. 37:561–565. 2016. View Article : Google Scholar : PubMed/NCBI

17 

Ma Z, Wang Y, Piao T, Li Z, Zhang H, Liu Z and Liu J: The tumor suppressor role of PAQR3 in osteosarcoma. Tumour Biol. 36:3319–3324. 2015. View Article : Google Scholar : PubMed/NCBI

18 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

19 

Ling ZQ, Guo W, Lu XX, Zhu X, Hong LL, Wang Z, Wang Z and Chen Y: A Golgi-specific protein PAQR3 is closely associated with the progression, metastasis and prognosis of human gastric cancers. Ann Oncol. 25:1363–1372. 2014. View Article : Google Scholar : PubMed/NCBI

20 

Xie X, Zhang Y, Jiang Y, Liu W, Ma H, Wang Z and Chen Y: Suppressive function of RKTG on chemical carcinogen-induced skin carcinogenesis in mouse. Carcinogenesis. 29:1632–1638. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Porter AG and Jänicke RU: Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6:99–104. 1999. View Article : Google Scholar : PubMed/NCBI

22 

Oltvai ZN, Milliman CL and Korsmeyer SJ: Bcl-2 heterodimerizes in vivo with a conserved homolog, Bax, that accelerates programmed cell death. Cell. 74:609–619. 1993. View Article : Google Scholar : PubMed/NCBI

23 

Marshall CJ: Specificity of receptor tyrosine kinase signaling: Transient versus sustained extracellular signal-regulated kinase activation. Cell. 80:179–185. 1995. View Article : Google Scholar : PubMed/NCBI

24 

Zhao S, Konopleva M, Cabreira-Hansen M, Xie Z, Hu W, Milella M, Estrov Z, Mills GB and Andreeff M: Inhibition of phosphatidylinositol 3-kinase dephosphorylates BAD and promotes apoptosis in myeloid leukemias. Leukemia. 18:267–275. 2004. View Article : Google Scholar : PubMed/NCBI

25 

Gregorj C, Ricciardi MR, Petrucci MT, Scerpa MC, De Cave F, Fazi P, Vignetti M, Vitale A, Mancini M, Cimino G, et al: ERK1/2 phosphorylation is an independent predictor of complete remission in newly diagnosed adult acute lymphoblastic leukemia. Blood. 109:5473–5476. 2007. View Article : Google Scholar : PubMed/NCBI

26 

Milella M, Konopleva M, Precupanu CM, Tabe Y, Ricciardi MR, Gregorj C, Collins SJ, Carter BZ, D'Angelo C, Petrucci MT, et al: MEK blockade converts AML differentiating response to retinoids into extensive apoptosis. Blood. 109:2121–2129. 2007. View Article : Google Scholar : PubMed/NCBI

27 

Milella M, Kornblau SM, Estrov Z, Carter BZ, Lapillonne H, Harris D, Konopleva M, Zhao S, Estey E and Andreeff M: Therapeutic targeting of the MEK/MAPK signal transduction module in acute myeloid leukemia. J Clin Invest. 108:851–859. 2001. View Article : Google Scholar : PubMed/NCBI

28 

Jiang Y, Xie X, Zhang Y, Luo X, Wang X, Fan F, Zheng D, Wang Z and Chen Y: Regulation of G-protein signaling by RKTG via sequestration of the G betagamma subunit to the Golgi apparatus. Mol Cell Biol. 30:78–90. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Wu J, Wong WW, Khosravi F, Minden MD and Penn LZ: Blocking the Raf/MEK/ERK pathway sensitizes acute myelogenous leukemia cells to lovastatin-induced apoptosis. Cancer Res. 64:6461–6468. 2004. View Article : Google Scholar : PubMed/NCBI

30 

Martelli AM, Nyakern M, Tabellini G, Bortul R, Tazzari PL, Evangelisti C and Cocco L: Phosphoinositide 3-kinase/Akt signaling pathway and its therapeutical implications for human acute myeloid leukemia. Leukemia. 20:911–928. 2006. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Xu Y, Deng N, Wang X, Chen Y, Li G and Fan H: RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways. Oncol Lett 14: 965-970, 2017.
APA
Xu, Y., Deng, N., Wang, X., Chen, Y., Li, G., & Fan, H. (2017). RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways. Oncology Letters, 14, 965-970. https://doi.org/10.3892/ol.2017.6182
MLA
Xu, Y., Deng, N., Wang, X., Chen, Y., Li, G., Fan, H."RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways". Oncology Letters 14.1 (2017): 965-970.
Chicago
Xu, Y., Deng, N., Wang, X., Chen, Y., Li, G., Fan, H."RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways". Oncology Letters 14, no. 1 (2017): 965-970. https://doi.org/10.3892/ol.2017.6182
Copy and paste a formatted citation
x
Spandidos Publications style
Xu Y, Deng N, Wang X, Chen Y, Li G and Fan H: RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways. Oncol Lett 14: 965-970, 2017.
APA
Xu, Y., Deng, N., Wang, X., Chen, Y., Li, G., & Fan, H. (2017). RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways. Oncology Letters, 14, 965-970. https://doi.org/10.3892/ol.2017.6182
MLA
Xu, Y., Deng, N., Wang, X., Chen, Y., Li, G., Fan, H."RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways". Oncology Letters 14.1 (2017): 965-970.
Chicago
Xu, Y., Deng, N., Wang, X., Chen, Y., Li, G., Fan, H."RKTG overexpression inhibits proliferation and induces apoptosis of human leukemia cells via suppression of the ERK and PI3K/AKT signaling pathways". Oncology Letters 14, no. 1 (2017): 965-970. https://doi.org/10.3892/ol.2017.6182
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