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A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs

The membrane-anchored matrix metalloproteinase-regulator RECK is often down-regulated in various types of cancers; the levels of residual RECK in resected tumors often correlate with better prognosis. Forced expression of RECK in cancer cells suppresses tumor angiogenesis, invasion, and metastasis i...

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Autores principales: Murai, Ryuya, Yoshida, Yoko, Muraguchi, Teruyuki, Nishimoto, Emi, Morioka, Yoko, Kitayama, Hitoshi, Kondoh, Shinae, Kawazoe, Yoshinori, Hiraoka, Masahiro, Uesugi, Motonari, Noda, Makoto
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248105/
https://www.ncbi.nlm.nih.gov/pubmed/21304177
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author Murai, Ryuya
Yoshida, Yoko
Muraguchi, Teruyuki
Nishimoto, Emi
Morioka, Yoko
Kitayama, Hitoshi
Kondoh, Shinae
Kawazoe, Yoshinori
Hiraoka, Masahiro
Uesugi, Motonari
Noda, Makoto
author_facet Murai, Ryuya
Yoshida, Yoko
Muraguchi, Teruyuki
Nishimoto, Emi
Morioka, Yoko
Kitayama, Hitoshi
Kondoh, Shinae
Kawazoe, Yoshinori
Hiraoka, Masahiro
Uesugi, Motonari
Noda, Makoto
author_sort Murai, Ryuya
collection PubMed
description The membrane-anchored matrix metalloproteinase-regulator RECK is often down-regulated in various types of cancers; the levels of residual RECK in resected tumors often correlate with better prognosis. Forced expression of RECK in cancer cells suppresses tumor angiogenesis, invasion, and metastasis in xenograft models. RECK is therefore a promising marker for benignancy and a potential effector in cancer therapy. We established a cell line containing two transgene systems: (1) the secreted alkaline phosphatase (SEAP) gene fused to Reck promoter and (2) the HRAS(12V) oncogene driven by the Tet-off promoter system. This cell line exhibits transformed phenotype in regular medium and flat morphology with increased SEAP activity in the presence of doxycycline, allowing the assessment of RECK-inducing activity of chemicals in the contexts of both transformed and untransformed cells. Our pilot experiments with 880 known bioactive compounds detected 34 compounds that activate RECK promoter; among these, 10 were authentic anticancer drugs. Four selected compounds up-regulated endogenous RECK protein in several human cancer cell lines. The top-ranking compound, disulfiram, strongly suppressed spontaneous lung-metastasis of human fibrosarcoma cells in nude mice. Our data demonstrate the value of this screen in discovering effective cancer therapeutics.
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spelling pubmed-32481052012-01-18 A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs Murai, Ryuya Yoshida, Yoko Muraguchi, Teruyuki Nishimoto, Emi Morioka, Yoko Kitayama, Hitoshi Kondoh, Shinae Kawazoe, Yoshinori Hiraoka, Masahiro Uesugi, Motonari Noda, Makoto Oncotarget Research Papers The membrane-anchored matrix metalloproteinase-regulator RECK is often down-regulated in various types of cancers; the levels of residual RECK in resected tumors often correlate with better prognosis. Forced expression of RECK in cancer cells suppresses tumor angiogenesis, invasion, and metastasis in xenograft models. RECK is therefore a promising marker for benignancy and a potential effector in cancer therapy. We established a cell line containing two transgene systems: (1) the secreted alkaline phosphatase (SEAP) gene fused to Reck promoter and (2) the HRAS(12V) oncogene driven by the Tet-off promoter system. This cell line exhibits transformed phenotype in regular medium and flat morphology with increased SEAP activity in the presence of doxycycline, allowing the assessment of RECK-inducing activity of chemicals in the contexts of both transformed and untransformed cells. Our pilot experiments with 880 known bioactive compounds detected 34 compounds that activate RECK promoter; among these, 10 were authentic anticancer drugs. Four selected compounds up-regulated endogenous RECK protein in several human cancer cell lines. The top-ranking compound, disulfiram, strongly suppressed spontaneous lung-metastasis of human fibrosarcoma cells in nude mice. Our data demonstrate the value of this screen in discovering effective cancer therapeutics. Impact Journals LLC 2010-08-06 /pmc/articles/PMC3248105/ /pubmed/21304177 Text en Copyright: © 2010 Murai et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited
spellingShingle Research Papers
Murai, Ryuya
Yoshida, Yoko
Muraguchi, Teruyuki
Nishimoto, Emi
Morioka, Yoko
Kitayama, Hitoshi
Kondoh, Shinae
Kawazoe, Yoshinori
Hiraoka, Masahiro
Uesugi, Motonari
Noda, Makoto
A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
title A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
title_full A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
title_fullStr A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
title_full_unstemmed A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
title_short A novel screen using the Reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
title_sort novel screen using the reck tumor suppressor gene promoter detects both conventional and metastasis-suppressing anticancer drugs
topic Research Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3248105/
https://www.ncbi.nlm.nih.gov/pubmed/21304177
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