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

Yutaka Fujisue, Takatoshi Nakagawa, Kiyoshi Takahara, Teruo Inamoto, Satoshi Kiyama, Haruhto Azuma, Michio Asahi

Research output: Contribution to journalArticle

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Abstract

Erythropoietin (Epo) is a potent inducer of erythro-poiesis 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.

Original languageEnglish
Pages (from-to)1765-1770
Number of pages6
JournalOncology Letters
Volume5
Issue number6
DOIs
Publication statusPublished - 01-06-2013

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Hypoxia-Inducible Factor 1
Erythropoietin
Renal Cell Carcinoma
Cell Proliferation
Cell Line
Erythropoietin Receptors
Kidney
Small Interfering RNA

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Fujisue, Yutaka ; Nakagawa, Takatoshi ; Takahara, Kiyoshi ; Inamoto, Teruo ; Kiyama, Satoshi ; Azuma, Haruhto ; Asahi, Michio. / Induction of erythropoietin increases the cell proliferation rate in a hypoxia-inducible factor-1-dependent and -independent manner in renal cell carcinoma cell lines. In: Oncology Letters. 2013 ; Vol. 5, No. 6. pp. 1765-1770.
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abstract = "Erythropoietin (Epo) is a potent inducer of erythro-poiesis 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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Induction of erythropoietin increases the cell proliferation rate in a hypoxia-inducible factor-1-dependent and -independent manner in renal cell carcinoma cell lines. / Fujisue, Yutaka; Nakagawa, Takatoshi; Takahara, Kiyoshi; Inamoto, Teruo; Kiyama, Satoshi; Azuma, Haruhto; Asahi, Michio.

In: Oncology Letters, Vol. 5, No. 6, 01.06.2013, p. 1765-1770.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Induction of erythropoietin increases the cell proliferation rate in a hypoxia-inducible factor-1-dependent and -independent manner in renal cell carcinoma cell lines

AU - Fujisue, Yutaka

AU - Nakagawa, Takatoshi

AU - Takahara, Kiyoshi

AU - Inamoto, Teruo

AU - Kiyama, Satoshi

AU - Azuma, Haruhto

AU - Asahi, Michio

PY - 2013/6/1

Y1 - 2013/6/1

N2 - Erythropoietin (Epo) is a potent inducer of erythro-poiesis 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.

AB - Erythropoietin (Epo) is a potent inducer of erythro-poiesis 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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