Project/Area Number |
13670182
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Human pathology
|
Research Institution | Sapporo Medical University |
Principal Investigator |
ICHIMIYA Shingo Sapporo Medical University School of Medicine, Department of Pathology, Assistant Professor, 医学部, 講師 (30305221)
|
Co-Investigator(Kenkyū-buntansha) |
SATO Noriyuki Sapporo Medical University School of Medicine, Department of Pathology, Professor, 医学部, 教授 (50158937)
|
Project Period (FY) |
2001 – 2003
|
Project Status |
Completed (Fiscal Year 2003)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2002: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2001: ¥1,400,000 (Direct Cost: ¥1,400,000)
|
Keywords | p73 / p53 / cell cycle / thymic epithelial cell / immune regulation / p53ファミリー |
Research Abstract |
Accumulating evidence has demonstrated that the gene encoding p73, a molecule homologous to the archetypal tumor suppressor p53, knows infrequent mutation in various human malignancies unlike p53. Together with functional similarities of p73 to p53, we hypothesized that tumor cell growth might be controlled when an intrinsic p73 of tumor cells could be up-regulated by hitherto unknown mechanism. To elucidate the mechanism, we have newly made antibodies specific to p73 and analyzed a series of human tissues. Results indicated that p73 was specifically localized at the nuclei of thymic medullary epithelial cells, but not in cortical epithelium. Moreover, in vitro studies using thymic epithelial cell lines showed that p73 was potentially involved regulation of M-CSF as well as GM-CSF. It is well known that in medullary epithelium foster dendritic cells and macrophages for establishing negative selection of immature T cells in the region. Thus, these imply that p73 in the medulla might have important roles, to control stromal cells for negative selection. We also investigated a. molecule specifically regulating the expression of p73 from biologically active molecules of natural resources in collaboration with the Institute of Marine Bioscience of our university. Currently, we have found a. certain fraction of the Aristertoles of. sea urchin has a capacity to up-regulating p73 of human thymic epithelial cells. We would like to further clarify the expression mechanism of p73 and develop its related methodology for controlling tumor cell cycle as well as tumor immunity possibly through the activation of antigen presenting cells.
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