2004 Fiscal Year Final Research Report Summary
Identification of novel therapeutic target genes for renal cell carcinoma
| Project/Area Number |
15591693
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Urology
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| Research Institution | Kochi Medical School Kochi UNIVERSITY |
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Principal Investigator |
OKUDA Heiwa Kochi Medical School, Research Associate, 医学部, 助手 (60325420)
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| Co-Investigator(Kenkyū-buntansha) |
SHUIN Taro Kochi Medical School, Professor, 医学部, 教授 (80179019)
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| Project Period (FY) |
2003 – 2004
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| Keywords | VHL / RCC / methylation |
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| Research Abstract |
The purpose of this research is to identify novel therapeutic target genes which related to renal carcinogenesis.
VHL tumor suppressor protein functions as ubiquitin ligase in cells. However, which intracellular signaling pathways were affected by pVHL depletion was largely unknown. Tb elucidate the gene expression profiles associated with VHL mutations, we transfected a pVHL null RCC cell line with plasmids expressing wild-type pVHL or pVHL bearing point mutations related to each subtype of VHL disease, and then subjected to microarray analysis. Expression profiling showed that the location of pVHL mutations results in distinct gene expression patterns. We found the TGFBI gene was up-regulated in type-1 VHL disease associated mutant and the SFN and LOXL1 genes were down-regulated in type-2B VHL disease associated mutant. Real-time PCR analysis confirmed the altered expression of these selected genes in the clones.
Since some tumor suppressor genes are frequently inactivated by epigenetic alterations, we next applied methylated CpG island amplification/representational difference analysis (MCA/RDA) to isolate differentially methylated CpG islands in renal cell carcinoma. We found one of the isolated CpG islands (MIRC9) was tumor specifically methylated in primary renal cancer with high frequency. Furthermore, re-expression of MIRC9 in RCC cell line, which lack MIRC9 expression, suppressed its growth and induced apoptosis. These results suggest that MIRC9 may act as tumor suppressor gene.
In this study, we newly identified several genes which show tumor specific altered expression or aberrant methylation, and these genes may be novel therapeutic targets in renal cell carcinoma.
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[Journal Article] Downregulation of CAP43 gene by von Hippel-Lindau tumor suppressor protein in human renal cancer cells2003
Author(s)
Masuda K, Ono M, Okamoto M, Morikawa W, Otsubo M, Migita T, Tsuneyoshi M, Okuda H, Shuin T, Naito S, Kuwano M
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Journal Title
International Journal of Cancer 105
Pages: 803-810
Description
「研究成果報告書概要(欧文)」より
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