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Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
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Expression of Ets-1 in human clear cell renal cell carcinomas: implications for angiogenesis

Shuji Mikami1, Mototsugu Oya, Ryuichi Mizuno

  • 1Division of Diagnostic Pathology, School of Medicine, Keio University Hospital, 35 Shinanomachi, Tokyo, 160-8582, Japan.

Cancer Science
|July 22, 2006
PubMed

Insights

Ets-1 expression is elevated in clear cell renal cell carcinoma (RCC) and correlates with increased microvessel density, suggesting its role in tumor angiogenesis. Hypoxia upregulates both Ets-1 and vascular endothelial growth factor (VEGF) in RCC.

Area of Science:

  • Oncology
  • Molecular Biology
  • Pathology

Background:

  • Vascular endothelial growth factor (VEGF) is implicated in the high angiogenesis of renal cell carcinoma (RCC).
  • The role of Ets-1, a VEGF target molecule, in RCC angiogenesis remains largely uncharacterized.

Purpose of the Study:

  • To investigate the expression of Ets-1 and VEGF in different RCC subtypes.
  • To evaluate the correlation between Ets-1 expression, VEGF, and microvessel density (MVD) in RCC.
  • To explore the regulatory role of hypoxia on Ets-1 and VEGF expression in RCC.

Main Methods:

  • Immunohistochemistry was used to detect Ets-1 and VEGF protein expression.
  • Reverse transcription-polymerase chain reaction (RT-PCR) assessed mRNA levels of Ets-1 and VEGF.
  • Microvessel density (MVD) was quantified to assess tumor angiogenesis.
  • RCC cell lines were subjected to hypoxic conditions to study gene expression regulation.

Main Results:

  • Ets-1 was localized in carcinoma and endothelial cells of clear cell RCC, but not papillary RCC.
  • Both immunohistochemical Ets-1 expression and MVD were significantly higher in clear cell RCC compared to papillary RCC.
  • RT-PCR confirmed predominant Ets-1 mRNA expression in clear cell RCC, correlating directly with MVD.
  • Hypoxic treatment upregulated Ets-1 and VEGF mRNA expression in clear cell RCC-derived cell lines.

Conclusions:

  • Ets-1 is expressed in human clear cell RCC and its expression is associated with increased angiogenesis.
  • Ets-1 may play a significant role in the angiogenesis of clear cell RCC.
  • Hypoxia is identified as a key regulator of Ets-1 and VEGF expression in clear cell RCC.

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