Funktionelle Charakterisierung des Trefoil Factor 1 im Pankreaskarzinom

Die Familie der Trefoil Faktoren umfasst drei kleine, proteasestabile Proteine. Sie sind maßgeblich an der Restitution des Gastrointestinaltraktes beteiligt und beeinflussen somit unter anderem Prozesse der Migration und Apoptose. Es konnte gezeigt werden, dass ein Mitglied dieser Familie, der Trefo...

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Bibliographic Details
Main Author: Schmidt, Manuela
Contributors: Buchholz, Malte (Dr.) (Thesis advisor)
Format: Doctoral Thesis
Published: Philipps-Universität Marburg 2011
Online Access:PDF Full Text
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The Trefoil Factor Family consists of three small, protease-resistant proteins which play a crucial role in the restitution of the gastrointestinal tract. In this context, they influence such important processes as migration and apoptosis. So far, it could be shown that one member of this family, the Trefoil Factor 1 (TFF1), is overexpressed in pancreatic ductal adenocarcinoma and its precursor lesions. For the first time, this study examines the functional role of TFF1 in pancreatic cancer. During the search for a pair of cell lines in which one partner shows a high and the other one a low TFF1-expression, PaTu 8988s and PaTu 8988t were identified. In the following expreriments, the influence of TFF1 on proliferation, apoptosis, migration and anchorage-independent cell growth was tested. TFF1 expression was altered by either suppressing TFF1 by siRNA transfection or stable overexpression of TFF1. As a result, it was observed that TFF1 has a pro-migratory and anti-proliferative effect on pancreatic carcinoma cell lines. At the same time, similar experiments were conducted with HEK-293-cells which transiently overexpressed TFF1. In this cell lineage, deriving from human embryonic kidney, TFF1 enhances proliferation and anchorage-independent growth. In summary, it can be said that TFF1 seems to support the oncogenic potential of human pancreatic carcinoma cells. Interestingly, it could be shown that TFF1 has different effects on proliferation in different cell lines. Further research has to be conducted to elucidate those findings. Furthermore, other aspects of malignant growth, like effects on invasion, should be examined.