1997 Fiscal Year Final Research Report Summary
Application of a new tumor cell motility stimulating factor, PD-I family proteins todiagnosis and treatment of cancer.
| Project/Area Number |
08670177
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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 |
Pathological medical chemistry
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| Research Institution | Kobe University |
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Principal Investigator |
SANO Kimihiko Kobe University School of Medicine Department of Pediatrics, Assistant Professor, 医学部, 講師 (40205993)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Ecto-enzyme / Phosohodiesterase I / Nucleotide pyrophosphatase / Tumor metastasis / Motility / In situ hybridization |
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| Research Abstract |
I have cloned two new members belonging to a phosphodiesterase I gene fimily from rat, and designated as PD-Ialpha and-beta. In current study I have cloned human PD-Ialpha and -beta and peroformed further analysis. I have found that human PD-Ialpha is an alternative splicing product of autotaxin, which is a newly found autocrine tumor cell motility-stimulating factor. I examined the expression of human PD-Ialpha/ATX gene in human neuroblastoma tumor tissues, motility stimulating activity of recombinant ATX on neuroblastoma cells, and investigated its transcriptional regulatory mechanism in a human neuroblastoma cell line. PD-Ialpha/ATX gene was expressed in the primary tumor tissues from the neuroblastoma patients at a various extent. This gene is also expressed in a SMS-KAN neuroblastoma cell line. We indentified both isoforms, PD-Ialpha and ATX,in these tumor tissues and SMS-KAN cells. The recombinant ATX stimulated the motility of SMS-KAN cells at low nanomolar concentration. We situated the promoter region, which is essential for its transcription in SMS-KAN cells, at-287 nt to -254 nt by the promoter activity assay. The gel shift assay revealed that there exists a nuclear protein in SMS-KAN cells that binds this region. These new insights about autocrine tumor cell motility-stimulating protein will help us to understand the metastatic mechanism of human neuroblastoma.
I have also cloned human PD-Ibeta. PD-Ibeta gene expression was mostly observed in the prostate and uterus. I have also shown that PD-Ialpha and beta are localized to human chromosome 8q24.1 and 6q22, respectively.
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[Publications] Nakamura, F., Tatsumi, E., Tani, A., Kumagai, S., Kosaka, S., Sano, K., Nakamura, H., Nesumi, N., Abe, T., and Koiwai, O.: "Coexpression of cell-surface immunoglobulin (sIg), terminal deoxynucleotidyl transferase (TdT) and recombination activating gene1 (RAG-1) : two cases and derived cell lines." Leukemia. 10. 1159-1163 (1996)
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[Publications] Tani, A., Tatsumi, E., Nakamura, F., Kumagai, S., Kosaka, Y., Sano, K., Nakamura, H., Amakawa, R., and Ohno, H.: "Sensitivity to dexamethasone and absence of bcl-2 protein in Burkitt's lymphoma cell line (Black93) derived from a patient with acute tumor lysis syndrome : comparative study with other BL and non-BL lines." Leukemia. 10. 1592-1603 (1996)
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[Publications] Hasegawa, D., Kojima, S., Tatsumi, E., Kosaka, Y., Nakamura, H., Sako, M., Osugi, Y., Nagata, S., and Sano, K.: "Elevation of the serum Fas ligand in patients with hemophagocytic syndrome and Diamond-Blackfan anemia." Blood. (in press). (1998)
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「研究成果報告書概要(欧文)」より
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[Publications] Sano, K., Goji, J., Kosaka, Y., Nakamura, H., Nakamura, F., and Tatsumi, E: "t (10 ; 12) (q24 ; q15) in a T-cell lymphoblastic lymphoma with myeloid hyperplasia." Cancer Genet.Cytogenet. (in press). (1998)
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「研究成果報告書概要(欧文)」より
