Murine pancreatic tumor cell line TD2 bears the characteristic pattern of genetic changes with two independently amplified gene loci.
TGFalpha/p53(+/-) transgenic mice represent a genetically engineered mouse model for pancreatic adenocarcinoma. The tumors develop a characteristic pattern of secondary genetic changes. From one of these tumors, the permanent cell line TD2 was established. Here, we describe in detail the genetic changes by molecular-cytogenetic techniques. The original tumor-specific CGH profile has been retained unchanged. The most characteristic aberration pattern bears chromosome 11. Egfr, localized on proximal chromosome 11, is amplified two to three times and leads to an easily identifiable, stable marker chromosome with a large amplification unit, which is present in each metaphase. The wild-type p53 gene on distal chromosome 11 is lost. The p16Ink4a locus on chromosome 4 is hypermethylated. For c-Myc a 15-fold amplification, present in a 1.65 Mb amplification unit, is detected on chromosome 15. Transition between presence in the form of several double minutes, DMs, or a single homogeneously staining region, HSR, was observed for c-Myc. Molecular-cytogenetic analysis of both amplification units show that Egfr amplification and c-Myc amplification represent two alternative modes by which genes get amplified in tumor cells. The expression level of the respective genes was proven by Northern blot analysis. The cell line TD2 represents a valuable in vitro model for pancreatic adenocarcinoma.
Schreiner
Bettina
B
Department of Human Genetics, University of Ulm, D-89069 Ulm, Germany.
Greten
Florian R
FR
Baur
Dorotthe M
DM
Fingerle
Alexander A
AA
Zechner
Ulrich
U
Böhm
Christian
C
Schmid
Michael
M
Hameister
Horst
H
Schmid
Roland M
RM
D000818:Animals; D015152:Blotting, Northern; D022202:Chromosomes, Artificial, Bacterial; D003582:Cytogenetics; D004247:DNA / Q000096:biosynthesis / Q000378:metabolism; D019175:DNA Methylation; D066246:ErbB Receptors / Q000378:metabolism; D015723:Gene Library; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D008957:Models, Genetic; D009693:Nucleic Acid Hybridization; D010190:Pancreatic Neoplasms / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D016271:Proto-Oncogene Proteins c-myc; D004247:DNA; D066246:ErbB Receptors