128P - Modulation of specificity protein 1 (SP1) is a novel therapeutic strategy for pancreatic cancer

Abstract

Pancreatic cancer is one of the most aggressive and lethal malignancies. Specificity Protein 1 (SP1) is a transcription factor regulates and promotes tumor progression. Some studies have reported SP1 promotes epithelial-mesenchymal transition (EMT) and is associated with aggressive and poor patient prognosis. However, there is a paucity of clinical evidence regarding the role of SP1 in pancreatic cancer. In this study, we aimed to confirm the function of SP1 in invasiveness of pancreatic cancer cells and to evaluate the clinical impact in patients with pancreatic cancer. Between June 2002 and December 2012, 81 patients underwent radical curative resection for pancreatic cancer at Gangnam Severance Hospital, Seoul, Korea. Pancreatic cancer cell lines MIA PaCa-2, PANC-1, AsPC-1, and BxPC-3 were used for in vitro study. To evaluate the endogenous expression level of SP1, we purified the whole RNA and protein to perform the qPCR, RT-PCR and Western blot. si-SP1 was used for specifically inhibit the function of SP1. The invasive potential of pancreatic cancer cells were assessed in matrigel coated chambers. Among the 81 patients, 32 (39.5%) were positive for SP1. On univariate and multivariate analyses, poor differentiation tumor and SP1-positive status were identified as independent prognostic factors for DFS. High expression of SP1 was observed and correlated with the expression of mesenchymal markers (Snail, L1CAM, Vimentin) unlike epithelial markers (CDH1). Importantly, silencing of SP1 showed markedly decrease in motility and the invasiveness of cancer cells (p < 0.001) as determined from transwell invasion and transendothelial migration assays, respectively. Our results demonstrated that SP1 is an independent marker for metastatic disease and death in patients with pancreatic cancer. Additionally, our in vitro study demonstrated that SP1 expression promotes EMT and the invasiveness of pancreatic cancer cell lines, a finding compatible with the results of previous in vitro studies. These findings suggest that SP1 can potentially be a valuable target for the improvement of survival rates in patients with pancreatic cancer.