Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer

Emerging evidence indicates that peroxisome proliferator-activated receptor γ (PPARγ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPARγ, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients...

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Main Authors: Valerio Pazienza, Francesca Tavano, Giorgia Benegiamo, Manlio Vinciguerra, Francesca Paola Burbaci, Massimiliano Copetti, Fabio Francesco di Mola, Angelo Andriulli, Pierluigi di Sebastiano
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2012/461784
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author Valerio Pazienza
Francesca Tavano
Giorgia Benegiamo
Manlio Vinciguerra
Francesca Paola Burbaci
Massimiliano Copetti
Fabio Francesco di Mola
Angelo Andriulli
Pierluigi di Sebastiano
author_facet Valerio Pazienza
Francesca Tavano
Giorgia Benegiamo
Manlio Vinciguerra
Francesca Paola Burbaci
Massimiliano Copetti
Fabio Francesco di Mola
Angelo Andriulli
Pierluigi di Sebastiano
author_sort Valerio Pazienza
collection DOAJ
description Emerging evidence indicates that peroxisome proliferator-activated receptor γ (PPARγ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPARγ, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPARγ activation on DNMTs expression in PC cell lines. qRT-PCR analysis showed that DNMT3B expression was downregulated in tumors compared to normal tissues (𝑃=0.03), whereas PPARγ and DNMT1 levels did not show significant alterations in PC patients. Expression levels between PPARγ and DNMT1 and between DNMT1 and DNMT3B were highly correlated (𝑃=0.008 and 𝑃=0.05 resp.). DNMT3B overexpression in tumor tissue was positively correlated with both lymph nodes spreading (𝑃=0.046) and resection margin status (𝑃=0.04), and a borderline association with perineural invasion (𝑃=0.06) was found. Furthermore, high levels of DNMT3B expression were significantly associated with a lower mortality in the whole population (HR=0.485; 95%CI=0.262–0.895, 𝑃=0.02) and in the subgroup of patients without perineural invasion (HR=0.314; 95%CI=0.130–0.758; 𝑃=0.01), while such association was not observed in patients with tumor invasion into perineural structures (𝑃=0.70). In conclusion, in vitro and in vivo PPARγ and DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior.
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spelling doaj-art-967f67403bb34ae0bcb496e7bd9a658c2025-02-03T06:08:35ZengWileyPPAR Research1687-47571687-47652012-01-01201210.1155/2012/461784461784Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic CancerValerio Pazienza0Francesca Tavano1Giorgia Benegiamo2Manlio Vinciguerra3Francesca Paola Burbaci4Massimiliano Copetti5Fabio Francesco di Mola6Angelo Andriulli7Pierluigi di Sebastiano8Division and Laboratory of Gastroenterology Unit, “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale dei Cappuccini n.1, 71013 San Giovanni Rotondo, ItalyDivision of Abdominal Surgery, “Casa Sollievo della Sofferenza” IRCCS Hospital, 71013 San Giovanni Rotondo, ItalyDivision and Laboratory of Gastroenterology Unit, “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale dei Cappuccini n.1, 71013 San Giovanni Rotondo, ItalyThe Foundation for Liver Research, c/o The Institute of Hepatology, 69-75 Chenies Mews, London WC1E 6HX, UKDivision of Abdominal Surgery, “Casa Sollievo della Sofferenza” IRCCS Hospital, 71013 San Giovanni Rotondo, ItalyBiostatistic Unit, “Casa Sollievo della Sofferenza” IRCCS Hospital, 71013 San Giovanni Rotondo, ItalyDivision of Abdominal Surgery, “Casa Sollievo della Sofferenza” IRCCS Hospital, 71013 San Giovanni Rotondo, ItalyDivision and Laboratory of Gastroenterology Unit, “Casa Sollievo della Sofferenza” IRCCS Hospital, Viale dei Cappuccini n.1, 71013 San Giovanni Rotondo, ItalyDivision of Abdominal Surgery, “Casa Sollievo della Sofferenza” IRCCS Hospital, 71013 San Giovanni Rotondo, ItalyEmerging evidence indicates that peroxisome proliferator-activated receptor γ (PPARγ) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPARγ, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPARγ activation on DNMTs expression in PC cell lines. qRT-PCR analysis showed that DNMT3B expression was downregulated in tumors compared to normal tissues (𝑃=0.03), whereas PPARγ and DNMT1 levels did not show significant alterations in PC patients. Expression levels between PPARγ and DNMT1 and between DNMT1 and DNMT3B were highly correlated (𝑃=0.008 and 𝑃=0.05 resp.). DNMT3B overexpression in tumor tissue was positively correlated with both lymph nodes spreading (𝑃=0.046) and resection margin status (𝑃=0.04), and a borderline association with perineural invasion (𝑃=0.06) was found. Furthermore, high levels of DNMT3B expression were significantly associated with a lower mortality in the whole population (HR=0.485; 95%CI=0.262–0.895, 𝑃=0.02) and in the subgroup of patients without perineural invasion (HR=0.314; 95%CI=0.130–0.758; 𝑃=0.01), while such association was not observed in patients with tumor invasion into perineural structures (𝑃=0.70). In conclusion, in vitro and in vivo PPARγ and DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior.http://dx.doi.org/10.1155/2012/461784
spellingShingle Valerio Pazienza
Francesca Tavano
Giorgia Benegiamo
Manlio Vinciguerra
Francesca Paola Burbaci
Massimiliano Copetti
Fabio Francesco di Mola
Angelo Andriulli
Pierluigi di Sebastiano
Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
PPAR Research
title Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
title_full Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
title_fullStr Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
title_full_unstemmed Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
title_short Correlations among PPAR𝜸, DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
title_sort correlations among ppar𝜸 dnmt1 and dnmt3b expression levels and pancreatic cancer
url http://dx.doi.org/10.1155/2012/461784
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