Genes and Proteins Differentially Expressed during In Vitro Malignant Transformation of Bovine Pancreatic Duct Cells1

• Published in: Neoplasia (New York, N.Y.) Vol. 9; no. 2; pp. 136 - 146
• Main Authors: Jesnowski, R, Zubakov, Dmitri, Faissner, Ralf, Ringel, Jörg, Hoheisel, Jörg D, Lösel, Ralf, Schnölzer, Martina, Löhr, Matthias
• Format: Journal Article
• Language: English
• Published: Neoplasia Press Inc 01-02-2007
• ISSN: 1522-8002; 1476-5586

Pancreatic carcinoma has an extremely bad prognosis due to lack of early diagnostic markers and lack of effective therapeutic strategies. Recently, we have established an
in vitro
model recapitulating the first steps in the carcinogenesis of the pancreas. SV40 large T antigen-immortalized bovine pancreatic duct cells formed intrapancreatic adenocarcinoma tumors on
k-ras
mut
transfection after orthotopic injection in the nude mouse pancreas. Here we identified genes and proteins differentially expressed in the course of malignant transformation using reciprocal suppression subtractive hybridization and 2D gel electrophoresis and mass spectrometry, respectively. We identified 34 differentially expressed genes, expressed sequence tags, and 15 unique proteins. Differential expression was verified for some of the genes or proteins in samples from pancreatic carcinoma. Among these genes and proteins, the majority had already been described either to be influenced by a mutated
ras
or to be differentially expressed in pancreatic adenocarcinoma, thus proving the feasibility of our model. Other genes and proteins (e.g.,
BBC1, GLTSCR2
, and
rhoGDIα
), up to now, have not been implicated in pancreatic tumor development. Thus, we were able to establish an
in vitro
model of pancreatic carcinogenesis, which enabled us to identify genes and proteins differentially expressed during the early steps of malignant transformation.