1997 Fiscal Year Final Research Report Summary
Active Elimination of Amplified Oncogenes from Tumor Cells
| Project/Area Number |
07044271
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| Research Category |
Grant-in-Aid for international Scientific Research
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| Allocation Type | Single-year Grants |
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| Section | Joint Research |
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| Research Field |
Molecular biology
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
UTIYAMA Hiroyasu HIROSHIMA UNIVERSITY,FAC.OF INTEG.ARTS SCIENCES,PROFESSOR, 総合科学部, 教授 (80025957)
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| Co-Investigator(Kenkyū-buntansha) |
HIRANO Tetsuo HIROSHIMA UNIVERSITY,FAC.OF INTEG.ARTS AND SCIENCES,RESEARCH ASSOCIATE, 総合科学部, 助手 (50228805)
SHIMIZU Noriaki HIROSHIMA UNIVERSITY,FAC.OF INTEG.ARTS AND SCIENCES,ASSOCIATE PROFESSOR, 総合科学部, 助教授 (10216096)
WAHL Geoffrey.M. THE SALK INSTITUTE FOR BIOLOGICAL STUDIES GENE EXPRESSION LAB,PROFESSOR, Professor
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| Project Period (FY) |
1995 – 1997
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| Keywords | Gene Amplification / Double Minute / Micronucleus / Nuclear Budding / Nuclear Structure / DNA replication / DM elimination / Lamin |
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| Research Abstract |
Tumor cells revert to normal phenotype or differentiate if the amplified oncogenes on DMs are eliminated from the cells. During the priod that was supported by this grant, we could deepen the understandings on both of the step that DMs are selectively incorporated into cytoplasmic micronuclei, and on the step that such micronuclei are extruded from the cells. On the former issue, we found that DMs locate at the periphery of G1-phase nuclei, and that these DMs are selectively incorporated into micronuclei formed during the S-phase by the nuclear budding process. This process was activated by the inactivation of p53 tumor suppressor protein. The paper describing these points is now in press at The Journal of Cell Biology. Furthermore, by the result from the research on this fiscal year, we could clarify the interesting intranuclear movement of DMs in relation to the replication at the periphearl heterochromatin. We could also clarify the mechanism of budding formation through the finding that peripheral DMs are partitioned by the nuclear lamin structure. The papers describing these points are now in prepeartion. On the other hand, we could found that micronuclei enriched in DMs are extruded from the cells, and showed this process should be one of the key process that should be targeted by the DM-elimination therapy. During this fiscal year, we found that these extracellular micronuclei have normal cytoplasmic membrane as well as nucelar membrane, and that the DNA in the extracellular micronuclei do not suffer an extensive degradation. A paper describing these point is also in preparation. It was thought that DMs may be tranfered from donor cells to acceptor cells by the mediation of extracellular micronuclei. We have analyzed this point, and got an evidence on the DM-tranfer, but found these cells ceased growing. The research to clarify this point is currently undergoing.
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