Die epithelial-mesenchymale Transition beim Pankreaskarzinom: Expression und Rolle der Transkriptionsfaktoren Snail, Slug und Twist

Abstract

Epithelial to mesenchymal transitions are vital for tumor growth and metastasis. Several inducers of EMT are transcription factors that repress E-cadherin expression such as Snail, Slug and Twist. In this study we aimed to examine the expression of these transcription factors in pancreatic cancer. The expression of Snail, Slug, and Twist, was detected by immunohistochemistry in tissue samples from patients with pancreatic ductal adenocarcinoma. Four human pancreatic cancer cell lines (Capan-1, HPAF-2, MIAPaCa-2, and Panc-1) were analyzed by RT-PCR, real-time PCR and western blotting. An orthotopic nude mouse model of pancreatic cancer was applied for in vivo experiments. 78 % of human pancreatic cancer tissues showed an expression of Snail, and 50 % of the patients displayed positive expression of Slug. Twist showed no or only weak expression. Snail expression was higher in undifferentiated cancer cell lines (MIAPaCa-2, Panc-1) than in more differentiated cell lines (Capan-1, HPAF-2) and correlated positively with the metastatic potential of the cancer cells in the animal model. Expression of Slug was detected in all cell lines with different intensities. Twist was not expressed. The transcription factors Snail and Slug are expressed in pancreatic cancer but not in normal tissue suggesting a role in the progression of human pancreatic tumors.