AbstractsBiology & Animal Science

Human PDAC is one of the most devastating diseases without effective therapy strategy so far. Although PDCA may not directly depend on estrogen, it was found to be an estrogen-related malignancy. In breast cancer, ligand-activated ERα moves from the cytoplasm to the nucleus of cancer cells, increases the expression of MTA3 and modulates EMT via the transcription factor Snail and the adhesion molecule E-cadherin. To date, this EMT-related signaling pathway has not been investigated in human PDAC. In this study, the prior knowledge about the expression patterns of ERα and the downstream regulation elements MTA3, Snail, and E-cadherin in human PDAC tissues, human pancreatic cancer cell lines and the corresponding xenograft animal model were studied. The results indicated that ERα, MTA3, Snail, and E-cadherin were present in human PDAC tissues, with most of ERα expression in the cytoplasm of the tumor cells instead of the nucleus. The expression patterns of these factors in 5 human pancreatic cancer cell lines, ASPC-1, Capan-1, HPAF-2, MiaPaCa-2 and PANC-1, and the human breast cancer cell line MCF-7 as a control was investigated in the next step. At mRNA level, all cell lines displayed ERα expression, at the protein level only weak expression was detected in the cytoplasm as well as in the nucleus of pancreatic cancer cells due to estrogenic stimulation in the cell culture media. The pancreatic cancer cell line Capan-1 displayed the expression patterns of all factors related to this pathway and will be used for further functional studies. The xenograft animal model of the five human PDAC cell lines showed similar expression patterns compared to the results of the cell culture experiments. In conclusion, the elements of the ERα mediated pathway are present in human pancreatic cancer cells, but the function remains unclear. Most of the ERα is detectable in the cytoplasm of human PDAC at an inactivated form, probably due to a lack of estrogen in the surrounding tissue. Based on these results, further experiments will be done to investigate the role of thissignal pathway in mediating EMT in human pancreatic cancer cells. Das duktale Adenokarzinom des Pankreas ist eine der verheerendsten Erkrankungen, für die es bisher keine effektive Behandlungsstrategie gibt. Obwohl es nicht direkt Östrogen-abhängig ist, wurde gezeigt, dass es ein Östrogen-assoziierter Tumor ist. Bei Brustkrebs bewegt sich liganden-aktivierter ERα aus dem Zytoplasma zum Zellkern von Tumorzellen, erhöht die Expression von MTA3 und moduliert die Epitheliale-Mesenchymale-Transformation (EMT) über den Transkriptionsfaktor Snail und das Adhesionsmolekül E-Cadherin. Bisher wurde dieser EMT-assoziierte Signalweg noch nicht im duktalen Adenokarzinom des Pankreas untersucht. In dieser Arbeit wurde zunächst das Expressionsmuster von ERα und der folgenden Regulationselemente MTA3, Snail und E-Cadherin in menschlichem Pankreaskarzinomgewebe, humanen Pankreaskarzinomzelllinien und dementsprechenden Xenograft Tiermodellen untersucht. Die Ergebnisse zeigten, dass ERα,…