High class I HDAC activity and expression are associated with RelA/p65 activation in pancreatic cancer <it>in vitro </it>and <it>in vivo</it>

• Main Authors: Neuhaus Peter, Bahra Marcus, Müller Berit, Noske Aurelia, Darb-Esfahani Silvia, Buckendahl Ann-Christin, Budczies Jan, Denkert Carsten, Lehmann Annika, Dietel Manfred, Kristiansen Glen, Weichert Wilko
• Format: Article
• Language: English
• Published: BMC 2009-11-01
• Series: BMC Cancer
• Online Access: http://www.biomedcentral.com/1471-2407/9/395

<p>Abstract</p> <p>Background</p> <p>The strong association between aberrant HDAC activity and the occurrence of cancer has led to the development of a variety of HDAC inhibitors (HDIs), which emerge as promising new targeted anticancer therapeutics.</p> <p>Methods</p> <p>Due to the pivotal role of RelA/p65 in the tumorigenesis of pancreatic neoplasia we examined the expression of class I HDACs 1, 2 and 3 in a large cohort of human pancreatic carcinomas and correlated our findings with RelA/p65 expression status. Furthermore, we investigated the impact of the HDIs SAHA and VPA on RelA/p65 activity in pancreatic cancer cell culture models.</p> <p>Results</p> <p>Class I HDACs were strongly expressed in a subset of pancreatic adenocarcinomas and high expression was significantly correlated with increased nuclear translocation of RelA/p65 (p = 0.024). The link of HDAC activity and RelA/p65 in this tumor entity was confirmed <it>in vitro</it>, where RelA/p65 nuclear translocation as well as RelA/p65 DNA binding activity could be markedly diminished by HDI treatment.</p> <p>Conclusion</p> <p>The RelA/p65 inhibitory effects of SAHA and VPA <it>in vitro </it>and the close relationship of class I HDACs and RelA/p65 <it>in vivo </it>suggest that treatment with HDIs could serve as a promising approach to suppress NF-κB activity which in turn may lead to enhanced apoptosis and chemosensitization of pancreatic cancers.</p>