1988 Fiscal Year Final Research Report Summary
Autocrine Proliferation and Differentiation-Capacities of Leukemic Cells, and Molecular Analyses of Leukemic Phenotypes
| Project/Area Number |
62480263
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
SAITO Masaki Jichi Medical School, Professor, 医学部, 教授 (60012762)
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| Co-Investigator(Kenkyū-buntansha) |
MOTOYOSHI Kazuo Jichi Medical School, Associate Professor, 医学部, 助教授 (80137702)
NAKAMURA Mitsuru Jichi Medical School, Associate, 医学部, 助手 (20198237)
FURUKAWA Yusuke Jichi Medical School, Associate, 医学部, 助手 (00199431)
OHTA Masatsugu Jichi Medical School, Lecturer, 医学部, 講師 (90160514)
KITAGAWA Sei-ichi Jichi Medical School, Lecturer, 医学部, 講師 (50133278)
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| Project Period (FY) |
1987 – 1988
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| Keywords | gene transfection / malignant phenotype / tumorigenicity / autocrine growth / electroporation / FCC-P2 / NFS-60 / エレクトロポレーション |
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| Research Abstract |
Normal hemopoietic progenitors proliferate and differentiate to produce mature functioning cells, depending on a variety of hemopoietic growth factors, of which genes have been recently cloned. In contrast, autocrine growth mechanism(s) have been proposed especially at the onset of leukemia, a type of hemopoietic malignancy, since leukemia have been considered to develop from the transformation and clonal proliferation of hemopoietic precursors. The concept of autocrine mechanism(s) of cellular proliferation suggests that a cell can both produce and respond to a particular growth factor. Then, under certain conditions, such a cell might become independent of external growth regulation in a manner that would lead to malignant transformation. In order to elucidate the mechanism of malignant transformation of hemopoietic cells, we investigated the tumorigenicity of FDC-P2, an IL-3-dependent murine myeloblastic cell line established from a long-term culture of normal bone marrow cells, aft
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er transfection of the cDNA encoding murine IL-3 by electroporation. Two sublines growing in the absence of growth factors were established. Southern blot analysis using the probe of IL-3 gene showed that one cell line contained one copy of the integrated IL-3 gene, and the other contained 2-3 copies. A significant amount of IL-3 was detected in cutured media of these cell lines. These results suggest that the expression of IL-3 gene and the secretion of IL-3 transformed IL-3-dependent cells to IL-3-independent cells. Subcutaneous transfer of these cells into nude mice consistently produced tumors. The capacity of the transfected cells producing IL-3 appeared to confer a tumorigenic phenotype to these cells. Similar results were obtained with another murine myelomonocytic cell line, NFS-60 cells. In the latter case, 10 clones which became independent of IL-3 were established after transfection with IL-3 gene into the parental IL-3-dependent cell line. The capacities to produce IL-3 outside the cell were varied with different clones. However, the IL-3 activity inside the cell was found not to be much less different among the clones. Thus, the intracellular IL-3 activity was considered to be crucial for the autocrine growth of the transformed cells produced by transfection of the growth factor gene. Less
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