Journal Article

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

Bahra, Marcus, Lehmann, Annika, Buckendahl, Ann-Christin, Denkert, Carsten, Dietel, Manfred, Noske, Aurelia, Neuhaus, Peter, Müller, Berit Maria, Kristiansen, Glen, Weichert, Wilko, Darb-Esfahani, Silvia, Budczies, Jan

2009

نظرة عامة

Background 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. Methods 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. Results 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 in vitro , where RelA/p65 nuclear translocation as well as RelA/p65 DNA binding activity could be markedly diminished by HDI treatment. Conclusion The RelA/p65 inhibitory effects of SAHA and VPA in vitro and the close relationship of class I HDACs and RelA/p65 in vivo 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.

• الناشر: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• موضوع: Acids / Adenocarcinoma - enzymology / Adenocarcinoma - genetics / Adenocarcinoma - metabolism / Adenocarcinoma - pathology / Adult / Aged / Aged, 80 and over / Apoptosis / Biomedical and Life Sciences / Biomedicine / Cancer / Cancer Research / Care and treatment / Cell adhesion & migration / Cell cycle / Cell Line, Tumor / Cell Nucleus - genetics / Cell Nucleus - metabolism / Cytokines / Development and progression / Enzyme Inhibitors - pharmacology / Female / Gene expression / Gene Expression - drug effects / Genetic aspects / Health Promotion and Disease Prevention / Histone Deacetylase 1 - genetics / Histone Deacetylase 1 - metabolism / Histone Deacetylase 2 - genetics / Histone Deacetylase 2 - metabolism / Histone Deacetylases - genetics / Histone Deacetylases - metabolism / Humans / Male / Medicine/Public Health / Middle Aged / Oncology / Pancreas / Pancreatic cancer / Pancreatic Neoplasms - enzymology / Pancreatic Neoplasms - genetics / Pancreatic Neoplasms - metabolism / Pancreatic Neoplasms - pathology / Pathology / Physiological aspects / Research Article / Surgical Oncology / Transcription Factor RelA - genetics / Transcription Factor RelA - metabolism / Transferases