Adult T-cell leukemia/lymphoma (ATLL) is an aggressive form of human leukemia/lymphoma. Although this disease is initiated by infection with human T-lymphotropic virus type 1 (HTLV-1), many HTLV-1 carriers survive for a long period without aggressive illness, suggesting that other factors may play roles in the progression of ATLL to an aggressive state. However, the mechanism involved in this progression still remains unclear. Previously, we have reported that ASY/Nogo mRNA was markedly down-regulated in human small-cell lung carcinomas, whereas it was expressed in normal tissues and other lung carcinomas, such as adenocarcinoma and squamous cell carcinoma. To understand whether or not ASY/Nogo gene is involved in the progression of ATLL, we examined the expression of ASY/Nogo mRNA in smoldering, chronic and aggressive ATLL, and found that the expression level of ASY/Nogo mRNA was markedly reduced in clinically aggressive ATLL. HTLV-1 Tax expression was not affected by the down-regulation of ASY/Nogo mRNA. These results indicate that the ASY/Nogo gene may act as a suppressor against ATLL progression, independent of Tax expression.
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http://dx.doi.org/10.1002/ijc.22011 | DOI Listing |
Carcinogenesis
April 2007
Department of Microbiology, Shiga University of Medical Science, Setatsukinowa-cho, Otsu, Shiga 520-2192, Japan.
The drs gene was originally isolated as a suppressor of v-src transformation. Expression of drs mRNA is markedly downregulated in a variety of human cancer cell lines and tissues, suggesting the potential role of this gene as a tumor suppressor. Previously, we found that Drs protein associates with ASY/Nogo-B/RTN-x(S), an apoptosis-inducing protein in the endoplasmic reticulum, and sequentially activates caspases to induce apoptosis in human cancer cells without involvement of the mitochondria.
View Article and Find Full Text PDFInt J Cancer
October 2006
Clinical Research Institute, National Hospital Organization, Osaka National Hospital, Chuo-ku, Osaka, Japan.
Adult T-cell leukemia/lymphoma (ATLL) is an aggressive form of human leukemia/lymphoma. Although this disease is initiated by infection with human T-lymphotropic virus type 1 (HTLV-1), many HTLV-1 carriers survive for a long period without aggressive illness, suggesting that other factors may play roles in the progression of ATLL to an aggressive state. However, the mechanism involved in this progression still remains unclear.
View Article and Find Full Text PDFOncogene
April 2004
Department of Microbiology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
The drs gene was originally isolated as a suppressor against v-src transformation. Expression of drs mRNA was markedly downregulated in a variety of human cancer cell lines and tissues, suggesting that the drs gene acts as a tumor suppressor. In this study, we found that ectopic expression of the Drs protein induced apoptosis in human cancer cell lines.
View Article and Find Full Text PDFApoptosis
January 2003
Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita 565-0871, Japan.
ASY, also designated Nogo, RTN-X, or RTN4, is a reticulon family protein containing two transmembrane domains and a C-terminal double lysine endoplasmic reticulum (ER) retrieval motif. Three protein variants are synthesized from the cognate mRNAs produced by alternative splicing, and are expressed in almost all tissues, localizing predominantly in the ER. The ASY protein induces apoptosis in various cancer cells when overexpressed, whereas normal cells are relatively resistant to ASY-dependent apoptosis.
View Article and Find Full Text PDFOncogene
July 2001
Department of Tumor Virology, Research Institute for Microbial Diseases, Osaka University, Suita 565-0871, Japan.
Although apoptosis plays an essential role in the embryogenesis and homeostasis of multicellular organisms, this mechanism has not yet been fully clarified. We isolated a novel human apoptosis-inducing gene, ASY, which encodes an endoplasmic reticulum-targeting protein without any known apoptosis-related motifs. This gene is identical to the Nogo-B, a splice variant of the Nogo-A which has recently been shown to be an inhibitor of neuronal regeneration in the central nervous system.
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