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Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion

BACKGROUND: We have previously shown that Matrix metalloproteinase (MMP) -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA) increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR c...

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Autores principales: Staun-Ram, Elsebeth, Goldman, Shlomit, Shalev, Eliezer
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2009
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787504/
https://www.ncbi.nlm.nih.gov/pubmed/19939245
http://dx.doi.org/10.1186/1477-7827-7-135
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author Staun-Ram, Elsebeth
Goldman, Shlomit
Shalev, Eliezer
author_facet Staun-Ram, Elsebeth
Goldman, Shlomit
Shalev, Eliezer
author_sort Staun-Ram, Elsebeth
collection PubMed
description BACKGROUND: We have previously shown that Matrix metalloproteinase (MMP) -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA) increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR choriocarcinoma cell-line and 6-8 w first trimester trophoblasts. METHODS: The effect of Forskolin (PKA) on MMP-2 expression was assessed by Northern Blot and RT-PCR. Possible transcription factors binding to consensus MMP-2 promoter sequences in response to Forskolin, were detected by EMSA binding assay and their expression assessed by western blot analysis. Antisense transfection of relevant transcription factors was performed and the inhibitory effect assessed on MMP-2 expression (RT-PCR), secretion (zymography) and trophoblast invasiveness (transwell migration assay). RESULTS: We found that Forskolin increased MMP-2 mRNA in JAR cells within 24 hours, and induced binding to p53, Ets, C/EBP and AP-2. Transcription factors Ets-2, phospho- p53, C/EBP epsilon, C/EBP lambda and AP-2 alpha bound to their respective binding sequences in response to Forskolin and the expressions of these transcription factors were all elevated in Forskolin- treated cells. Inhibition of Ets-2 and p53 reduced MMP-2 expression, secretion and invasiveness of Forskolin treated cells. CONCLUSION: MMP-2 is regulated by PKA through several binding sites and transcription factors including Ets-2, p53, C/EBP, C/EBP lambda and AP-2 alpha. Ets-2 and p53 mediate cAMP- induced trophoblast invasiveness, through regulation of MMP-2.
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spelling pubmed-27875042009-12-03 Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion Staun-Ram, Elsebeth Goldman, Shlomit Shalev, Eliezer Reprod Biol Endocrinol Research BACKGROUND: We have previously shown that Matrix metalloproteinase (MMP) -2 is a key-enzyme in early trophoblast invasion and that Protein Kinase A (PKA) increases MMP-2 expression and trophoblast invasion. The aim of this study was to examine MMP -2 regulation by PKA in invasive trophoblasts: JAR choriocarcinoma cell-line and 6-8 w first trimester trophoblasts. METHODS: The effect of Forskolin (PKA) on MMP-2 expression was assessed by Northern Blot and RT-PCR. Possible transcription factors binding to consensus MMP-2 promoter sequences in response to Forskolin, were detected by EMSA binding assay and their expression assessed by western blot analysis. Antisense transfection of relevant transcription factors was performed and the inhibitory effect assessed on MMP-2 expression (RT-PCR), secretion (zymography) and trophoblast invasiveness (transwell migration assay). RESULTS: We found that Forskolin increased MMP-2 mRNA in JAR cells within 24 hours, and induced binding to p53, Ets, C/EBP and AP-2. Transcription factors Ets-2, phospho- p53, C/EBP epsilon, C/EBP lambda and AP-2 alpha bound to their respective binding sequences in response to Forskolin and the expressions of these transcription factors were all elevated in Forskolin- treated cells. Inhibition of Ets-2 and p53 reduced MMP-2 expression, secretion and invasiveness of Forskolin treated cells. CONCLUSION: MMP-2 is regulated by PKA through several binding sites and transcription factors including Ets-2, p53, C/EBP, C/EBP lambda and AP-2 alpha. Ets-2 and p53 mediate cAMP- induced trophoblast invasiveness, through regulation of MMP-2. BioMed Central 2009-11-25 /pmc/articles/PMC2787504/ /pubmed/19939245 http://dx.doi.org/10.1186/1477-7827-7-135 Text en Copyright ©2009 Staun-Ram et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Staun-Ram, Elsebeth
Goldman, Shlomit
Shalev, Eliezer
Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion
title Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion
title_full Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion
title_fullStr Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion
title_full_unstemmed Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion
title_short Ets-2 and p53 mediate cAMP-induced MMP-2 expression, activity and trophoblast invasion
title_sort ets-2 and p53 mediate camp-induced mmp-2 expression, activity and trophoblast invasion
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2787504/
https://www.ncbi.nlm.nih.gov/pubmed/19939245
http://dx.doi.org/10.1186/1477-7827-7-135
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