Publications by authors named "Ryozo Moriuchi"

Myeloid ELF1-like factor (MEF/ELF4), a member of the ETS transcription factors, can function as an oncogene in murine cancer models and is overexpressed in various human cancers. Here, we report a mechanism by which MEF/ELF4 may be activated by a common leukemia-associated mutation in the nucleophosmin gene. By using a tandem affinity purification assay, we found that MEF/ELF4 interacts with multifactorial protein nucleophosmin (NPM1).

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We identified RECK, a membrane-anchored glycoprotein negatively regulating the activities of MMPs, as a molecule interacting with Tgat oncoprotein consisting of RhoGEF domain and the unique C-terminal 15 amino acids. The Tgat increased the invasive potential of NIH3T3 cells expressing endogenous mouse RECK and this effect was partially inhibited by the co-expression of human RECK. On the contrary, the expression of exogenous human RECK in HT1080 cell line lacking the endogenous RECK expression reduced its invasive activity, which was recovered by the Tgat co-expression.

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Constitutive activity of NF-kappaB is associated with various human cancers including adult T-cell leukemia (ATL). In this study, we have found Tgat that activates NF-kappaB by screening a cDNA expression library derived from ATL cells. We previously identified Tgat as the oncogene, which consists of the Rho-guanine nucleotide exchange factor (Rho-GEF) domain and the unique C-terminal region, as a consequence of alternative splicing of the Trio transcript.

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The human papillomavirus (HPV) E6 and E7 proteins play essential roles in HPV-associated cervical carcinogenesis. However, cells transformed by E6 or E7 rarely grow into tumors in nude mice, indicating that the carcinogenesis involves additional molecular events. The highly efficient retroviral cDNA expression system derived from HeLa cells identified two cDNA species coding NADH dehydrogenase 1 alpha subcomplex 5 (NDUFA5) and zinc finger protein 9 (ZNF9), exhibiting the potential to transform murine fibroblast cell line, NIH3T3.

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Pancreatic ductal carcinoma (PDC) remains one of the most intractable malignancies in humans. In order to clarify the molecular events underlying the carcinogenesis in PDC, we constructed a retroviral cDNA expression library from a PDC cell line, and used it to screen transforming genes in PDC by a focus formation assay with mouse 3T3 fibroblasts. We could obtain a total of 30 transformed cell foci in the screening, and one of the cDNA inserts harvested from such cell clones turned out to encode a wild-type human ARAF1.

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Aggressive natural killer cell leukemia (ANKL) is an intractable malignancy that is characterized by the outgrowth of NK cells. To identify transforming genes in ANKL, we constructed a retroviral cDNA expression library from an ANKL cell line KHYG-1. Infection of 3T3 cells with recombinant retroviruses yielded 33 transformed foci.

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Expression of inflammatory cytokines derived from Th1 cell population is increased in patients with human T-lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It has been shown that cytokine signaling molecules, including transcription factors T-bet and GATA-3, interleukin-12 receptor beta 2 (IL-12R beta 2) and suppressors of cytokine signaling (SOCS), such as SOCS1, are important in differentiation of naive T cells into Th1 helper T cells. To assess the immunological status from the stand-point of cytokine signaling in patients with HAM/TSP, we analyzed mRNA expression of these cytokine signaling molecules in peripheral blood mononuclear cells using quantitative RT-PCR.

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By screening cDNA expression libraries derived from fresh leukemic cells of adult T-cell leukemia for the potential to transform murine fibroblasts, NIH3T3, we have identified a novel transforming gene, designated Tgat. Expression of Tgat in NIH3T3 resulted in the loss of contact inhibition, increase of saturation density, anchorage-independent growth in a semisolid medium, tumorigenicity in nude mice, and increased invasiveness. Sequence comparison revealed that an alternative RNA splicing of the Trio gene was involved in the generation of Tgat.

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BACKGROUND: The clinical use of organs and cells of pig donors as a source of tissue for xenotransplantation and extracorporeal therapies has been problematic due to the risk for zoonotic infection of porcine endogenous retroviruses (PERV). METHODS: The effect of human serum on PERV was evaluated using an infectivity assay and virolysis assay. Cell-free PERV infection to human 293 cells was determined by the presence of proviruses 5 days post-infection by a highly sensitive nested PCR, and the lysis of PERV virions was determined by the reverse transcriptase activities released into the supernatant.

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In adult T-cell leukemia (ATL), tumor cells commonly express abundant membrane-bound Fas antigen. We reported a significant correlation between Fas expression status of ATL patients and their clinical outcome. In the current study, we analyzed the Fas cDNA sequence of the distinctive ATL cases that barely expressed mFas identified during the previous study.

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