Reduced expression of the membrane skeleton protein beta1-spectrin (SPTBN1) is associated with worsened prognosis in pancreatic cancer
Xiaohua Jiang1,2*, Sonja Gillen1*, Irene Esposito3,4, Nathalia A. Giese5, Christoph W. Michalski1, Helmut Friess1 and Jörg Kleeff1,6
1Department of General Surgery, Technische Universität München, Munich, Germany, 2Department of General Surgery, Zhong-Da Hospital, Southeast University, Nanjing, China, 3Institute of Pathology, Technische Universität München, Munich, Germany, 4Institute of Pathology, Helmholtz Zentrum München, Oberschleissheim, Germany, 5Department of General Surgery, University of Heidelberg, Heidelberg, Germany and 6Center of Cancer Systems Biology, Department of Medicine, Caritas St. Elizabeth's Medical Center, Tufts University School of Medicine, Boston, MA, USA
*These authors contributed equally to the manuscript.
Offprint requests to: Jörg Kleeff, MD, Department of Surgery, Technische Universität München, Ismaningerstrasse 22, 81675 Munich, Germany. e-mail: firstname.lastname@example.org; email@example.com
Summary. Spectrins are members of the superfamily of F-actin cross linking proteins that are important as scaffolding proteins for protein sorting, cell adhesion, and migration. In addition, spectrins have been implicated in TGF-beta signaling. The aim of the present study was to analyze the expression and localization of beta1-spectrin (SPTBN1) in pancreatic tissues. mRNA levels of SPTBN1 in cultured pancreatic cancer cell lines, as well as in normal pancreatic tissues (n=18), chronic pancreatitis (n=48) and pancreatic cancer tissues (n=66) were analyzed by real time quantitative RT-PCR. Localization of SPTBN1 in pancreatic tissues was determined by immunohistochemistry. SPTBN1 staining was assessed semi-quantitatively in 55 cancer tissues and survival analysis was carried out using the Kaplan-Meier method. Median SPTBN1 mRNA levels were 6.0-fold higher in pancreatic cancer tissues compared to the normal pancreas (p<0.0001) and 2.2fold higher compared to chronic pancreatitis tissues (p=0.0002). In the normal pancreas, SPTBN1 was present in the cytoplasm of normal ductal cells and occasionally in pancreatic acinar and centroacinar cells. In pancreatic cancer tissues, SPTBN1 was present in the cytoplasm of pancreatic cancer cells. Low SPTBN1 protein expression indicated a tendency for worsened prognosis with a median survival of 14.0 months, versus 23.8 months for patients whose tumors expressed moderate/high levels of SPTBN1. In conclusion, reduced SPTBN1 expression correlated with shorter survival of pancreatic cancer patients, suggesting a tumor suppressor function of this gene, as has already been shown for other malignancies of the gastrointestinal tract. Histol Histopathol 25, 1497-1506 (2010)
Key words: ELF, Cytoskeleton, TGF-ß, Smad, Pancreatic cancer