%0 Journal Article
%T Correlations among PPAR , DNMT1, and DNMT3B Expression Levels and Pancreatic Cancer
%A Valerio Pazienza
%A Francesca Tavano
%A Giorgia Benegiamo
%A Manlio Vinciguerra
%A Francesca Paola Burbaci
%A Massimiliano Copetti
%A Fabio Francesco di Mola
%A Angelo Andriulli
%A Pierluigi di Sebastiano
%J PPAR Research
%D 2012
%I Hindawi Publishing Corporation
%R 10.1155/2012/461784
%X Emerging evidence indicates that peroxisome proliferator-activated receptor ¦Ã (PPAR¦Ã) and DNA methyltransferases (DNMTs) play a role in carcinogenesis. In this study we aimed to evaluate the expression of PPAR¦Ã, DNMT1, and DNMT3B and their correlation with clinical-pathological features in patients with pancreatic cancer (PC), and to define the effect of PPAR¦Ã activation on DNMTs expression in PC cell lines. qRT-PCR analysis showed that DNMT3B expression was downregulated in tumors compared to normal tissues ( ), whereas PPAR¦Ã and DNMT1 levels did not show significant alterations in PC patients. Expression levels between PPAR¦Ã and DNMT1 and between DNMT1 and DNMT3B were highly correlated ( and resp.). DNMT3B overexpression in tumor tissue was positively correlated with both lymph nodes spreading ( ) and resection margin status ( ), and a borderline association with perineural invasion ( ) was found. Furthermore, high levels of DNMT3B expression were significantly associated with a lower mortality in the whole population ( 95% ¨C0.895, ) and in the subgroup of patients without perineural invasion ( ; 95% ¨C0.758; ), while such association was not observed in patients with tumor invasion into perineural structures ( ). In conclusion, in vitro and in vivo PPAR¦Ã and DNMTs appear interrelated in PC, and this interaction might influence cell phenotype and disease behavior. 1. Introduction Pancreatic cancer (PC) is ranked as the fourth leading cause of cancer-related deaths worldwide [1, 2]. It is highly aggressive and resistant to chemotherapy, and our inability to detect it at an early stage and the lack of effective systemic therapies are responsible for nearly identical incidence and mortality rates [3, 4]. More effective treatments and/or development of novel strategies are needed to improve the prognosis for patients with PC. The peroxisome proliferator-activated receptors (PPARs) belong to the nuclear receptor superfamily and are considered master regulators of lipid and glucose metabolism by transducing metabolic and nutritional signals into transcriptional responses [5, 6]. Three subtypes of PPARs are known: PPAR¦Á, PPAR¦Ä, and PPAR¦Ã [7]. The latter has been implicated in the pathology of numerous diseases including obesity, diabetes, atherosclerosis, and cancer. PPAR¦Ã ligands induce differentiation of liposarcoma cells and have a variety of antitumor effects also in pancreatic cancer cells [8]. The availability of such high-affinity ligands has facilitated the study of the signalling pathways through which PPAR¦Ã regulates metabolic processes, which are
%U http://www.hindawi.com/journals/ppar/2012/461784/