Expression of Ets-1 in human clear cell renal cell carcinomas: implications for angiogenesis.
Expression of vascular endothelial growth factor (VEGF) has been reported in renal cell carcinoma (RCC), a highly angiogenic carcinoma. However, little or no information is available on the expression of Ets-1, which is one of the target molecules of VEGF. In the present study, we examined the expression of Ets-1 and VEGF in RCC by immunohistochemistry and reverse transcription-polymerase chain reaction (RT-PCR), and correlations between expression and the microvessel density (MVD) were evaluated. Ets-1 was immunolocalized to carcinoma cells and endothelial cells of the microvessels in clear cell RCC, but not in papillary RCC. Immunohistochemical Ets-1 expression and MVD were significantly higher in clear cell RCC than in papillary RCC. Predominant mRNA expression of Ets-1 in clear cell RCC was confirmed by RT-PCR. The expression of Ets-1 correlated directly with MVD in clear cell RCC. Hypoxic treatment upregulated the mRNA expression of Ets-1 and VEGF in cell lines derived from clear cell RCC, suggesting that hypoxia is a key regulator for these molecules. These results demonstrate the expression of Ets-1 in human clear cell RCC and suggest the possibility that Ets-1 is involved in angiogenesis in clear cell RCC.
Mikami
Shuji
S
Division of Diagnostic Pathology, School of Medicine, Keio University Hospital, 35 Shinanomachi, Tokyo, 160-8582, Japan.
Oya
Mototsugu
M
Mizuno
Ryuichi
R
Murai
Masaru
M
Mukai
Makio
M
Okada
Yasunori
Y
D002292:Carcinoma, Renal Cell / Q000378:metabolism* / Q000473:pathology; D015687:Cell Hypoxia / Q000502:physiology; D045744:Cell Line, Tumor; D042783:Endothelial Cells / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007680:Kidney Neoplasms / Q000378:metabolism* / Q000473:pathology; D009389:Neovascularization, Pathologic / Q000503:physiopathology*; D050784:Proto-Oncogene Protein c-ets-1 / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis
C494041:ETS1 protein, human; D050784:Proto-Oncogene Protein c-ets-1; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A