High class I HDAC activity and expression are associated with RelA/p65 activation in pancreatic cancer in vitro and in vivo
1 Institute of Pathology, Charité University Hospital, Berlin, Germany
2 Department of General, Visceral, and Transplantation Surgery, Charité University Hospital, Berlin, Germany
3 Institute of Surgical Pathology - University Hospital, Zurich, Switzerland
BMC Cancer 2009, 9:395 doi:10.1186/1471-2407-9-395Published: 13 November 2009
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.
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.
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.
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.