We examined the effect of blocking the erythropoietin (Epo) signaling using an anti-Epo antibody, soluble form of Epo receptor (sEpoR) capable of binding to Epo or EpoR antagonist, and proved to be effective against x...We examined the effect of blocking the erythropoietin (Epo) signaling using an anti-Epo antibody, soluble form of Epo receptor (sEpoR) capable of binding to Epo or EpoR antagonist, and proved to be effective against xenografts of female reproductive organ malignancies and of cancer cell lines in nude mice. We transfected seven cancer cell lines of various origins to express constitutively active sEpoR, and examined their tumorigenesis in nude mice. Suppression of the tumor growth, decrease in viable and proliferating cells and reduction of vascular density were seen individually in all xenografts of transfected cell lines compared with the controls. Quantitative RT-PCR analyses showed that expression levels of Epo, EpoR, ?1A-adrenaline receptor (?1A-ADR) and muscalinic acetylcholine receptor subunit 3 mRNAs (m3-AchR) were higher in the majority of the wild-type xenografts than in the corresponding cell lines except for A549. In some of the transfected xenografts, EpoR, ?1A-ADR and m3-AchR mRNAs were down-regulated. Western blot analyses revealed that the constitutively activated ERK1/2MAPK was discernible in the majority of non-transfected cell lines and was reduced in the transfected cell lines. However, it was regained after exposure to acetylcholine and/or noradrenaline. These findings suggest that constitutively active sEpoR can effectively destroy the xenografts but signals from the autonomic neurotransmitters of the host produced under stress may interfere with this antitumor activity.展开更多
In eukaryotes, gene expression is achieved by four steps: transcription, processing, nuclear export, and translation. Each step requires multiple factors, and frequently two or more pathways are used by a single gene,...In eukaryotes, gene expression is achieved by four steps: transcription, processing, nuclear export, and translation. Each step requires multiple factors, and frequently two or more pathways are used by a single gene, enabling strictly regulated gene expression. Importantly, eukaryotes, taking advantage of the separated structures of the nucleus and the cytoplasm, have evolved complex and organized mRNA processing mechanisms that permit sophisticated biological activity. The processes are much more complicated than those found in prokaryotes, in which transcription and translation occur linearly in time and place. Here, we review gene expression, focusing on mRNA processing in the nucleus and the gene regulatory systems found at each step. Combination of gene regulation shows the typical phenotype in each cell. Further understanding of the uncertain mechanisms will uncover the gene regulation through mRNA expression.展开更多
文摘We examined the effect of blocking the erythropoietin (Epo) signaling using an anti-Epo antibody, soluble form of Epo receptor (sEpoR) capable of binding to Epo or EpoR antagonist, and proved to be effective against xenografts of female reproductive organ malignancies and of cancer cell lines in nude mice. We transfected seven cancer cell lines of various origins to express constitutively active sEpoR, and examined their tumorigenesis in nude mice. Suppression of the tumor growth, decrease in viable and proliferating cells and reduction of vascular density were seen individually in all xenografts of transfected cell lines compared with the controls. Quantitative RT-PCR analyses showed that expression levels of Epo, EpoR, ?1A-adrenaline receptor (?1A-ADR) and muscalinic acetylcholine receptor subunit 3 mRNAs (m3-AchR) were higher in the majority of the wild-type xenografts than in the corresponding cell lines except for A549. In some of the transfected xenografts, EpoR, ?1A-ADR and m3-AchR mRNAs were down-regulated. Western blot analyses revealed that the constitutively activated ERK1/2MAPK was discernible in the majority of non-transfected cell lines and was reduced in the transfected cell lines. However, it was regained after exposure to acetylcholine and/or noradrenaline. These findings suggest that constitutively active sEpoR can effectively destroy the xenografts but signals from the autonomic neurotransmitters of the host produced under stress may interfere with this antitumor activity.
文摘In eukaryotes, gene expression is achieved by four steps: transcription, processing, nuclear export, and translation. Each step requires multiple factors, and frequently two or more pathways are used by a single gene, enabling strictly regulated gene expression. Importantly, eukaryotes, taking advantage of the separated structures of the nucleus and the cytoplasm, have evolved complex and organized mRNA processing mechanisms that permit sophisticated biological activity. The processes are much more complicated than those found in prokaryotes, in which transcription and translation occur linearly in time and place. Here, we review gene expression, focusing on mRNA processing in the nucleus and the gene regulatory systems found at each step. Combination of gene regulation shows the typical phenotype in each cell. Further understanding of the uncertain mechanisms will uncover the gene regulation through mRNA expression.
