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Article

Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines

  • Authors:
    • Yutaka Fujisue
    • Takatoshi Nakagawa
    • Kiyoshi Takahara
    • Teruo Inamoto
    • Satoshi Kiyama
    • Haruhito Azuma
    • Michio Asahi
  • View Affiliations / Copyright

    Affiliations: Department of Urology, Faculty of Medicine, Osaka Medical College, Takatsuki, Osaka 569‑8686, Japan, Department of Pharmacology, Faculty of Medicine, Osaka Medical College, Takatsuki, Osaka 569‑8686, Japan
  • Pages: 1765-1770
    |
    Published online on: April 3, 2013
       https://doi.org/10.3892/ol.2013.1283
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Abstract

Erythropoietin (Epo) is a potent inducer of erythropoiesis that is mainly produced in the kidney. Epo is expressed not only in the normal kidney, but also in renal cell carcinomas (RCCs). The aim of the present study was to gain insights into the roles of Epo and its receptor (EpoR) in RCC cells. The study used two RCC cell lines, Caki‑1 and SKRC44, in which Epo and EpoR are known to be highly expressed. The proliferation rate and expression level of hypoxia‑inducible factor‑1α (HIF‑1α) were measured prior to and following Epo treatment and under normoxic and hypoxic conditions. To examine whether HIF‑1α or Epo were involved in cellular proliferation during hypoxia, these proteins were knocked down using small interfering RNA (siRNA) in Caki‑1 and SKRC44 cells. The results demonstrated that Epo enhanced the proliferation of the Caki‑1 and SKRC44 cells. HIF‑1α expression was increased upon the induction of hypoxia in the Caki‑1 cells, but remained unaffected in the SKRC44 cells. The proliferation rate was increased under hypoxic conditions in the Caki‑1 cells, but was decreased in the SKRC44 cells. Under hypoxic conditions, the proliferation of the Caki‑1 cells was significantly reduced by the knock‑down of HIF‑1α or Epo, while the proliferation of the SKRC44 cells was significantly suppressed by the knock‑down of Epo, but not HIF‑1α. In conclusion, these data suggest that the induction of Epo may accelerate the proliferation of the RCC cell lines in either a HIF‑1α‑dependent or ‑independent manner.
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1 

Koury ST, Bondurant MC, Koury MJ and Semenza GL: Localization of cells producing erythropoietin in murine liver by in situ hybridization. Blood. 77:2497–2503. 1991.PubMed/NCBI

2 

Krantz SB: Erythropoietin. Blood. 77:419–434. 1991.PubMed/NCBI

3 

Youssoufian H, Longmore G, Neumann D, et al: Structure, function, and activation of the erythropoietin receptor. Blood. 81:2223–2236. 1993.PubMed/NCBI

4 

Sasaki R, Masuda S and Nagao M: Erythropoietin: multiple physiological functions and regulation of biosynthesis. Biosci Biotechnol Biochem. 64:1775–1793. 2000. View Article : Google Scholar : PubMed/NCBI

5 

Winkelmann JC: The human erythropoietin receptor. Int J Cell Cloning. 10:254–261. 1992. View Article : Google Scholar

6 

Vogt C, Pentz S and Rich IN: A role for the macrophage in normal hemopoiesis: III. In vitro and in vivo erythropoietin gene expression in macrophages detected by in situ hybridization. Exp Hematol. 17:391–397. 1989.PubMed/NCBI

7 

Anagnostou A, Liu Z, Steiner M, et al: Erythropoietin receptor mRNA expression in human endothelial cells. Proc Natl Acad Sci USA. 91:3974–3978. 1994. View Article : Google Scholar : PubMed/NCBI

8 

Masuda S, Nagao M, Takahata K, et al: Functional erythropoietin receptor of the cells with neural characteristics. Comparison with receptor properties of erythroid cells. J Biol Chem. 268:11208–11216. 1993.

9 

Ogilvie M, Yu X, Nicolas-Metral V, et al: Erythropoietin stimulates proliferation and interferes with differentiation of myoblasts. J Biol Chem. 275:39754–39761. 2000. View Article : Google Scholar : PubMed/NCBI

10 

Yasuda Y, Masuda S, Chikuma M, et al: Estrogen-dependent production of erythropoietin in uterus and its implication in uterine angiogenesis. J Biol Chem. 273:25381–25387. 1998. View Article : Google Scholar : PubMed/NCBI

11 

Juul SE, Zhao Y, Dame JB, et al: Origin and fate of erythropoietin in human milk. Pediatr Res. 48:660–667. 2000. View Article : Google Scholar : PubMed/NCBI

12 

Trimble M, Caro J, Talalla A and Brain M: Secondary erythrocytosis due to a cerebellar hemangioblastoma: demonstration of erythropoietin mRNA in the tumor. Blood. 78:599–601. 1991.PubMed/NCBI

13 

Bruneval P, Sassy C, Mayeux P, et al: Erythropoietin synthesis by tumor cells in a case of meningioma associated with erythrocytosis. Blood. 81:1593–1597. 1993.PubMed/NCBI

14 

Yasuda Y, Musha T, Tanaka H, et al: Inhibition of erythropoietin signalling destroys xenografts of ovarian and uterine cancers in nude mice. Br J Cancer. 84:836–843. 2001. View Article : Google Scholar : PubMed/NCBI

15 

Acs G, Zhang PJ, Rebbeck TR, et al: Immunohistochemical expression of erythropoietin and erythropoietin receptor in breast carcinoma. Cancer. 95:969–981. 2002. View Article : Google Scholar : PubMed/NCBI

16 

Semenza GL: Hypoxia-inducible factor 1 and the molecular physiology of oxygen homeostasis. J Lab Clin Med. 131:207–214. 1998. View Article : Google Scholar : PubMed/NCBI

17 

Semenza GL: Hypoxia and cancer. Cancer Metastasis Rev. 26:223–224. 2007. View Article : Google Scholar

18 

Du R, Lu KV, Petritsch C, et al: HIF1alpha induces the recruitment of bone marrow-derived vascular modulatory cells to regulate tumor angiogenesis and invasion. Cancer Cell. 13:206–220. 2008. View Article : Google Scholar : PubMed/NCBI

19 

Powis G and Kirkpatrick L: Hypoxia inducible factor-1alpha as a cancer drug target. Mol Cancer Ther. 3:647–654. 2004.PubMed/NCBI

20 

Ihle JN, Witthuhn BA, Quelle FW, et al: Signaling by the cytokine receptor superfamily: JAKs and STATs. Trends Biochem Sci. 19:222–227. 1994. View Article : Google Scholar : PubMed/NCBI

21 

Mulcahy L: The erythropoietin receptor. Semin Oncol. 28(2 Suppl 8): 19–23. 2001. View Article : Google Scholar : PubMed/NCBI

22 

Leyland-Jones B: Trastuzumab: hopes and realities. Lancet Oncol. 3:137–144. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Westenfelder C and Baranowski RL: Erythropoietin stimulates proliferation of human renal carcinoma cells. Kidney Int. 58:647–657. 2000. View Article : Google Scholar : PubMed/NCBI

24 

Ito K, Yoshii H, Asano T, et al: Impact of increased erythropoietin receptor expression and elevated serum erythropoietin levels on clinicopathological features and prognosis in renal cell carcinoma. Exp Ther Med. 3:937–944. 2012.

25 

Laugsch M, Metzen E, Svensson T, et al: Lack of functional erythropoietin receptors of cancer cell lines. Int J Cancer. 122:1005–1011. 2008. View Article : Google Scholar : PubMed/NCBI

26 

Lee YS, Vortmeyer AO, Lubensky IA, et al: Coexpression of erythropoietin and erythropoietin receptor in von Hippel-Lindau disease-associated renal cysts and renal cell carcinoma. Clin Cancer Res. 11:1059–1064. 2005.PubMed/NCBI

27 

Maxwell PH and Ratcliffe PJ: Oxygen sensors and angiogenesis. Semin Cell Dev Biol. 13:29–37. 2002. View Article : Google Scholar : PubMed/NCBI

28 

Kaelin WG Jr: Molecular basis of the VHL hereditary cancer syndrome. Nat Rev Cancer. 2:673–682. 2002. View Article : Google Scholar : PubMed/NCBI

29 

Lee R, Kertesz N, Joseph SB, et al: Erythropoietin (Epo) and EpoR expression and 2 waves of erythropoiesis. Blood. 98:1408–1415. 2001. View Article : Google Scholar : PubMed/NCBI

30 

Mitjavila MT, Le Couedic JP, Casadevall N, et al: Autocrine stimulation by erythropoietin and autonomous growth of human erythroid leukemic cells in vitro. J Clin Invest. 88:789–797. 1991. View Article : Google Scholar : PubMed/NCBI

31 

Wang GL and Semenza GL: General involvement of hypoxia-inducible factor 1 in transcriptional response to hypoxia. Proc Natl Acad Sci USA. 90:4304–4308. 1993. View Article : Google Scholar : PubMed/NCBI

32 

Acs G, Chen M, Xu X, et al: Autocrine erythropoietin signaling inhibits hypoxia-induced apoptosis in human breast carcinoma cells. Cancer Lett. 214:243–251. 2004. View Article : Google Scholar : PubMed/NCBI

33 

Wincewicz A, Koda M, Sulkowska M, et al: STAT3 and hypoxia induced proteins - HIF-1alpha, EPO and EPOR in relation with Bax and Bcl-xL in nodal metastases of ductal breast cancers. Folia Histochem Cytobiol. 47:425–430. 2009.PubMed/NCBI

34 

Semenza GL: Targeting HIF-1 for cancer therapy. Nat Rev Cancer. 3:721–732. 2003. View Article : Google Scholar

35 

Semenza GL: Defining the role of hypoxia-inducible factor 1 in cancer biology and therapeutics. Oncogene. 29:625–634. 2010. View Article : Google Scholar : PubMed/NCBI

36 

McCarty MF: Barroso-Aranda J and Contreras F: Practical strategies for suppressing hypoxia-inducible factor activity in cancer therapy. Med Hypotheses. 74:789–797. 2010. View Article : Google Scholar : PubMed/NCBI

37 

Turner KJ, Moore JW, Jones A, et al: Expression of hypoxia-inducible factors in human renal cancer: relationship to angiogenesis and to the von Hippel-Lindau gene mutation. Cancer Res. 62:2957–2961. 2002.PubMed/NCBI

38 

Ohh M, Park CW, Ivan M, et al: Ubiquitination of hypoxia-inducible factor requires direct binding to the beta-domain of the von Hippel-Lindau protein. Nat Cell Biol. 2:423–427. 2000. View Article : Google Scholar : PubMed/NCBI

39 

Gong K, Zhang N, Zhang K and Na Y: The relationship of erythropoietin overexpression with von Hippel-Lindau tumour suppressor gene mutations between hypoxia-inducible factor-1α and -2α in sporadic clear cell renal carcinoma. Int J Mol Med. 26:907–912. 2010.PubMed/NCBI

40 

Motzer RJ, Escudier B, Oudard S, et al: Efficacy of everolimus in advanced renal cell carcinoma: a double-blind, randomized, placebo-controlled phase III trial. Lancet. 372:449–456. 2008. View Article : Google Scholar : PubMed/NCBI

41 

Miyazaki M, Yasuda M, Fujita M, et al: Therapeutic strategy targeting the mTOR–HIF-1α–VEGF pathway in ovarian clear cell adenocarcinoma. Path Int. 59:19–27. 2009.

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Copy and paste a formatted citation
Spandidos Publications style
Fujisue Y, Nakagawa T, Takahara K, Inamoto T, Kiyama S, Azuma H and Asahi M: Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines. Oncol Lett 5: 1765-1770, 2013.
APA
Fujisue, Y., Nakagawa, T., Takahara, K., Inamoto, T., Kiyama, S., Azuma, H., & Asahi, M. (2013). Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines. Oncology Letters, 5, 1765-1770. https://doi.org/10.3892/ol.2013.1283
MLA
Fujisue, Y., Nakagawa, T., Takahara, K., Inamoto, T., Kiyama, S., Azuma, H., Asahi, M."Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines". Oncology Letters 5.6 (2013): 1765-1770.
Chicago
Fujisue, Y., Nakagawa, T., Takahara, K., Inamoto, T., Kiyama, S., Azuma, H., Asahi, M."Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines". Oncology Letters 5, no. 6 (2013): 1765-1770. https://doi.org/10.3892/ol.2013.1283
Copy and paste a formatted citation
x
Spandidos Publications style
Fujisue Y, Nakagawa T, Takahara K, Inamoto T, Kiyama S, Azuma H and Asahi M: Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines. Oncol Lett 5: 1765-1770, 2013.
APA
Fujisue, Y., Nakagawa, T., Takahara, K., Inamoto, T., Kiyama, S., Azuma, H., & Asahi, M. (2013). Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines. Oncology Letters, 5, 1765-1770. https://doi.org/10.3892/ol.2013.1283
MLA
Fujisue, Y., Nakagawa, T., Takahara, K., Inamoto, T., Kiyama, S., Azuma, H., Asahi, M."Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines". Oncology Letters 5.6 (2013): 1765-1770.
Chicago
Fujisue, Y., Nakagawa, T., Takahara, K., Inamoto, T., Kiyama, S., Azuma, H., Asahi, M."Induction of erythropoietin increases the cell proliferation rate in a hypoxia‑inducible factor‑1‑dependent and ‑independent manner in renal cell carcinoma cell lines". Oncology Letters 5, no. 6 (2013): 1765-1770. https://doi.org/10.3892/ol.2013.1283
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