Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line

We previously demonstrated that a differentiation inducing drug, vesnarinone induced the growth arrest and p21(waf1) gene expression in a human salivary gland cancer cell line, TYS. In the present study, we investigated the mechanism of the induction of p21(waf1) gene by vesnarinone in TYS cells. We...

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Autores principales: Omotehara, F, Kawamata, H, Uchida, D, Hino, S, Nakashiro, K, Fujimori, T
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2002
Materias:
Experimental Therapeutics
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364327/
https://www.ncbi.nlm.nih.gov/pubmed/12434298
http://dx.doi.org/10.1038/sj.bjc.6600592
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author Omotehara, F
Kawamata, H
Uchida, D
Hino, S
Nakashiro, K
Fujimori, T
author_facet Omotehara, F
Kawamata, H
Uchida, D
Hino, S
Nakashiro, K
Fujimori, T
author_sort Omotehara, F
collection PubMed
description We previously demonstrated that a differentiation inducing drug, vesnarinone induced the growth arrest and p21(waf1) gene expression in a human salivary gland cancer cell line, TYS. In the present study, we investigated the mechanism of the induction of p21(waf1) gene by vesnarinone in TYS cells. We constructed several reporter plasmids containing the p21(waf1) promoter, and attempted to identify vesnarinone-responsive elements in the p21(waf1) promoter. By the luciferase reporter assay, we identified the minimal vesnarinone-responsive element in the p21(waf1) promoter at −124 to −61 relative to the transcription start site. Moreover, we demonstrated by electrophoretic mobility shift assay that Sp1 and Sp3 transcription factors bound to the vesnarinone-responsive element. Furthermore, we found that vesnarinone induced the histone hyperacetylation in TYS cells. These results suggest that vesnarinone directly activates p21(waf1) promoter via the activation of Sp1 and Sp3 transcription factors and the histone hyperacetylation in TYS cells. British Journal of Cancer (2002) 87, 1042–1046. doi:10.1038/sj.bjc.6600592 www.bjcancer.com © 2002 Cancer Research UK
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spelling pubmed-23643272009-09-10 Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line Omotehara, F Kawamata, H Uchida, D Hino, S Nakashiro, K Fujimori, T Br J Cancer Experimental Therapeutics We previously demonstrated that a differentiation inducing drug, vesnarinone induced the growth arrest and p21(waf1) gene expression in a human salivary gland cancer cell line, TYS. In the present study, we investigated the mechanism of the induction of p21(waf1) gene by vesnarinone in TYS cells. We constructed several reporter plasmids containing the p21(waf1) promoter, and attempted to identify vesnarinone-responsive elements in the p21(waf1) promoter. By the luciferase reporter assay, we identified the minimal vesnarinone-responsive element in the p21(waf1) promoter at −124 to −61 relative to the transcription start site. Moreover, we demonstrated by electrophoretic mobility shift assay that Sp1 and Sp3 transcription factors bound to the vesnarinone-responsive element. Furthermore, we found that vesnarinone induced the histone hyperacetylation in TYS cells. These results suggest that vesnarinone directly activates p21(waf1) promoter via the activation of Sp1 and Sp3 transcription factors and the histone hyperacetylation in TYS cells. British Journal of Cancer (2002) 87, 1042–1046. doi:10.1038/sj.bjc.6600592 www.bjcancer.com © 2002 Cancer Research UK Nature Publishing Group 2002-10-21 2002-10-21 /pmc/articles/PMC2364327/ /pubmed/12434298 http://dx.doi.org/10.1038/sj.bjc.6600592 Text en Copyright © 2002 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Experimental Therapeutics
Omotehara, F
Kawamata, H
Uchida, D
Hino, S
Nakashiro, K
Fujimori, T
Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line
title Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line
title_full Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line
title_fullStr Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line
title_full_unstemmed Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line
title_short Vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via Sp1 sites in a human salivary gland cancer cell line
title_sort vesnarinone, a differentiation inducing drug, directly activates p21(waf1) gene promoter via sp1 sites in a human salivary gland cancer cell line
topic Experimental Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2364327/
https://www.ncbi.nlm.nih.gov/pubmed/12434298
http://dx.doi.org/10.1038/sj.bjc.6600592
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