The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.

<h4>Background</h4>Recently, we established that a C>T single nucleotide polymorphism (SNP) in the promoter of the VEGF receptor FLT1 gene generates a (1/2) site p53 response element (RE-T) that results in p53 responsiveness of the promoter. The transcriptional control required an est...

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Autores principales:	Yari Ciribilli, Virginia Andreotti, Daniel Menendez, Jan-Stephan Langen, Gilbert Schoenfelder, Michael A Resnick, Alberto Inga
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2010
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/df11313559c046e288d78100b7f01f31
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spelling	oai:doaj.org-article:df11313559c046e288d78100b7f01f312021-12-02T20:11:52ZThe coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.1932-620310.1371/journal.pone.0010236https://doaj.org/article/df11313559c046e288d78100b7f01f312010-04-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/20422012/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Recently, we established that a C>T single nucleotide polymorphism (SNP) in the promoter of the VEGF receptor FLT1 gene generates a (1/2) site p53 response element (RE-T) that results in p53 responsiveness of the promoter. The transcriptional control required an estrogen receptor (ER) (1/2) site response element (ERE1) 225 nt upstream to the RE-T.<h4>Methodology/principal findings</h4>Here we report the identification of a second ER (1/2) site (ERE2) located 145 bp downstream of the RE-T and establish that both EREs can impact p53-mediated transactivation of FLT1-T in a manner that is cell type and ER level dependent. Gene reporter assays and ChIP experiments conducted in the breast cancer-derived MCF7 cells revealed that the ERE2 site was sufficient for p53-mediated ERalpha recruitment and transactivation of the FLT1-T promoter/reporter construct. Surprisingly, unlike the case for other p53 target promoters, p53-mediated transactivation of FLT1-T constructs or expression of the endogenous FLT1 gene, as well as binding of p53 and ER at the promoter constructs, was inducible by doxorubicin but not by 5-fluorouracil. Furthermore, ER activity at FLT1-T was differentially affected by ER ligands, compared to a control TFF1/pS2 ER target promoter. The p53-related transcription factors (TFs) p73 and p63 had no effect on FLT1 transactivation.<h4>Conclusions/significance</h4>We establish a new dimension to the p53 master regulatory network where p53-mediated transcription from a (1/2) site RE can be determined by ER binding at one or more cis-acting EREs in manner that is dependent on level of ER protein, the type of ER ligand and the specific p53-inducing agent.Yari CiribilliVirginia AndreottiDaniel MenendezJan-Stephan LangenGilbert SchoenfelderMichael A ResnickAlberto IngaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 5, Iss 4, p e10236 (2010)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yari Ciribilli Virginia Andreotti Daniel Menendez Jan-Stephan Langen Gilbert Schoenfelder Michael A Resnick Alberto Inga The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.
description	<h4>Background</h4>Recently, we established that a C>T single nucleotide polymorphism (SNP) in the promoter of the VEGF receptor FLT1 gene generates a (1/2) site p53 response element (RE-T) that results in p53 responsiveness of the promoter. The transcriptional control required an estrogen receptor (ER) (1/2) site response element (ERE1) 225 nt upstream to the RE-T.<h4>Methodology/principal findings</h4>Here we report the identification of a second ER (1/2) site (ERE2) located 145 bp downstream of the RE-T and establish that both EREs can impact p53-mediated transactivation of FLT1-T in a manner that is cell type and ER level dependent. Gene reporter assays and ChIP experiments conducted in the breast cancer-derived MCF7 cells revealed that the ERE2 site was sufficient for p53-mediated ERalpha recruitment and transactivation of the FLT1-T promoter/reporter construct. Surprisingly, unlike the case for other p53 target promoters, p53-mediated transactivation of FLT1-T constructs or expression of the endogenous FLT1 gene, as well as binding of p53 and ER at the promoter constructs, was inducible by doxorubicin but not by 5-fluorouracil. Furthermore, ER activity at FLT1-T was differentially affected by ER ligands, compared to a control TFF1/pS2 ER target promoter. The p53-related transcription factors (TFs) p73 and p63 had no effect on FLT1 transactivation.<h4>Conclusions/significance</h4>We establish a new dimension to the p53 master regulatory network where p53-mediated transcription from a (1/2) site RE can be determined by ER binding at one or more cis-acting EREs in manner that is dependent on level of ER protein, the type of ER ligand and the specific p53-inducing agent.
format	article
author	Yari Ciribilli Virginia Andreotti Daniel Menendez Jan-Stephan Langen Gilbert Schoenfelder Michael A Resnick Alberto Inga
author_facet	Yari Ciribilli Virginia Andreotti Daniel Menendez Jan-Stephan Langen Gilbert Schoenfelder Michael A Resnick Alberto Inga
author_sort	Yari Ciribilli
title	The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.
title_short	The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.
title_full	The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.
title_fullStr	The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.
title_full_unstemmed	The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.
title_sort	coordinated p53 and estrogen receptor cis-regulation at an flt1 promoter snp is specific to genotoxic stress and estrogenic compound.
publisher	Public Library of Science (PLoS)
publishDate	2010
url	https://doaj.org/article/df11313559c046e288d78100b7f01f31
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The coordinated p53 and estrogen receptor cis-regulation at an FLT1 promoter SNP is specific to genotoxic stress and estrogenic compound.

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