Analysis of p57KIP2 gene as tumor suppressor gene
| Project/Area Number |
16590970
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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 |
Hematology
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| Research Institution | National Hospital Organization, Nagoya Medical Center, Clinical Research Center |
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Principal Investigator |
NAGAI Hirokazu National Hospital Organization, Nagoya Medical Center, Clinical Research Center, Department of Blood Disease Research, Chief, 血液造血器疾患研究部, 部長 (30360811)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥1,700,000 (Direct Cost: ¥1,700,000)
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| Keywords | p57KIP2 / DNA methylation / siRNA / cDNA microarray / B Cell lymphoma / tumor suppressor gene / cDNA array |
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| Research Abstract |
Cell cycle is promoted by cyclin and cyclin dependent kinase (CDK), and suppressed by CDK inhibitor (CDKI). Once these genes were deregulated, cells might show aberrant proliferation, resulting in generation of tumors. We revealed that p57KIP2 gene, a kind of CDKI, was frequently inactivated by DNA methylation in lymphoid malignancies, especially B cell phenotype.
We knocked down p57KIP2 gene by introducing siRNA using a expression vector in the lymphoid cell line, NAMALWA. We could achieve 90% reduction of protein expression in this cell line. MTT assay showed that the growth of the p57KIP2 knockdown cell line was promoted comparing to the control cell line. And in the p57KLP2 knockdown cell line, the transition to S phase was also promoted. These findings indicated that the p57KIP2 gene is likely to be a potential tumor suppressor gene.
The difference of expression profiles between the p57KIP2 knockdown cell line and the control cell line were analyzed using cDNA microarray. We identified several genes, which were upregulated in the p57KIP2 knockdown cell line, and several genes, which were downregulated in the p57KIP2 knockdown cell line. Now, the functions of these genes are being investigated.
We also analyzed the correlation between p57KIP2 DNA methylation and clinical prognosis in B cell lymphoma. At this point, significant relationship between p57KIP2 DNA methylation and prognosis was not identified.
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Report
(3 results)
Research Products
(2 results)
