2002 Fiscal Year Final Research Report Summary
Alteration of expression profiling related the biological characteristics of renal cell carcinoma using cDNA microarray.
| Project/Area Number |
13671633
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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 | University of Tsukuba |
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Principal Investigator |
SHIMAZUI Toru Clin Med, Urology, Assoc Prof, 臨床医学系, 助教授 (80235613)
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| Co-Investigator(Kenkyū-buntansha) |
UCHIDA Kazuhiko Basic Med Sci, Molecular Oncol, Asso Prof, 基礎医学系, 助教授 (90211078)
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| Project Period (FY) |
2001 – 2002
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| Keywords | Renal cell carcinoma / Microarray / Expression profile / Interferon / Metastasis |
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| Research Abstract |
[Purpose] To evaluate the genomic background affecting clinical characteristics like metastasis, or response to treatment, we analyzed gene expression profiles of the renal cell carcinomas (RCCs) by microarray technology consisting of 4000 human cDNA clones using SKRC cell lines. Results consists of following 2 sections.
[Results] (1) To investigate the metastasis related characteristics, We compared gene expression profiles between RCC cell lines originated from primary or metastasis lesions with the normal renal proximal tubular cell line(RPTEC) as a control. The clustering with the selected 62 genes revealed similarity of profiling pattern between SKRC-17 and SKRC-29 cells which were derived from the metastatic lesion. Another line from metastatic lesion, SKRC-52, whose morphology showed unique spindle shape, had different pattern of expression profiling from the other cell lines. We found several genes up-regulated in the cell lines from the metastatic lesion. Unique profiling patte
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rn on gene expression clearly correlated to cell morphology and metastatic potential and these profiling might contribute to identify the genes involved in clinical characteristics of RCC. (2) Because response rate of interferon-alpha (IFN-a) against RCC is low, prediction of good candidates of IFN-a is required in terms of tailor-made treatment for patients with RCC. Six SKRC cell lines were selected as IFN-a-sensitive (SKRC-1, 14, 29, 59) or resistant (33, 52) cell line by means of MTT assay with addition of 1,000 to 10,000 IU/ml of IFN-a. Alteration of gene expression that differs between sensitive and resistant cell lines were confirmed using RT-PCR and Northern blot. Based on the alteration of expression between SKRC series and RPTEC, 1,401 genes were eventually selected. According to clustering analysis with these 1,401 genes, 6 cell lines could be divided into two groups, which were concordant with the sensitivity against IFN-a. In addition, remarkable alteration of gene expression between sensitive and resistant cell lines were observed in 10 genes, e.g. interferon regulatory factor 4. Microarray analysis provided a useful information concerning sensitivity of IFN-a in RCC cell lines. This clustering and/or expression pattern of selected gene set might be available to select patients who is IFN-a-responder. Less
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Research Products
(2 results)
