Genes and proteins differentially expressed during in vitro malignant transformation of bovine pancreatic duct cells.
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 rhoGDIalpha), 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.
Jesnowski
R
R
Clinical Cooperation Unit Molecular Gastroenterology (E180), German Cancer Research Center Heidelberg and Department of Medicine II, Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Germany. r.jesenofsky@dkfz.de
Zubakov
Dmitri
D
Faissner
Ralf
R
Ringel
Jörg
J
Hoheisel
Jörg D
JD
Lösel
Ralf
R
Schnölzer
Martina
M
Löhr
Matthias
M
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D021441:Carcinoma, Pancreatic Ductal / Q000378:metabolism* / Q000473:pathology; D002417:Cattle; D002461:Cell Line, Transformed / Q000378:metabolism; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D002472:Cell Transformation, Viral / Q000235:genetics; D002908:Chronic Disease; D018450:Disease Progression; D015180:Electrophoresis, Gel, Two-Dimensional; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000097:blood / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010183:Pancreatic Ducts / Q000166:cytology / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D010195:Pancreatitis / Q000235:genetics / Q000378:metabolism; D016133:Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D013382:Subtraction Technique
D000952:Antigens, Polyomavirus Transforming; D009363:Neoplasm Proteins