2003 Fiscal Year Final Research Report Summary

Regulation of neo-vascularization in human renal cell carcinoma by endothelium-specific transcription factors

Research Project

Project/Area Number	14571497
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Single-year Grants
Section	一般
Research Field	Urology
Research Institution	KYOTO UNIVERSITY
Principal Investigator	KAMOTO Toshiyuki KYOTO UNIVERSITY, Graduate School of Medicine, Associate Prof., 医学研究科, 助教授 (00281098)
Co-Investigator(Kenkyū-buntansha)	OGAWA Osamu KYOTO UNIVERSITY, Graduate School of Medicine, Professor, 医学研究科, 教授 (90260611) YAMADA Yoshihiro KYOTO UNIVERSITY, Graduate School of Medicine, Lecturer, 医学研究科, 講師 (30252464) ITO Noriyuki KYOTO UNIVERSITY, Graduate School of Medicine, Instructor, 医学研究科, 助手 (70343225) KINOSHITA Hidefumi KYOTO UNIVERSITY, Graduate School of Medicine, Instructor, 医学研究科, 講師 (30324635)
Project Period (FY)	2002 – 2003
Keywords	renal cell carcinoma / neovasculization / LMO2 / VEGF
Research Abstract	A number of transcription factors (LMO2,TAL1,GATA2,ID1,ETS1,and HIF2α), which play important roles in embryonic vasculogenesis/angiogenesis, have been identified chiefly using a gene knockout study. However, the regulation of neo-vascularization, such as angiogenesis associated with malignant tumor growth, remains obscure. In order to study the regulatory mechanism of tumor angiogenesis by these transcription factors, their expression level and pattern were studied in clear cell type renal cell carcinoma (ccRCC) (one of the most vascular-rich among human cancers) by reverse transcriptase-dependent PCR, western blot, or immunohistochemistry. All the transcription factors studied here were expressed in ccRCC in association with its blood vessels, and, among them, LMO2,TAL1,and ID1 showed endothelium-specific expression patterns. RCC with higher CD31 expression showed higher expression of these transcription factors. Reporter assay demonstrated that all these transcription factors activated FLK1 promoter/enhancer. Our study demonstrates that some of the transcription factors playing essential roles in embryonic angiogenesis are expressed in tumor blood vessels and may function by activating the vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathway.