Characterization of a newly established human pancreatic carcinoma cell line, UK Pan-1

BACKGROUND. A highly tumorigenic cell line designated as UK Pan-1 was estab lished in a surgically removed human pancreatic adenocarcinoma and characte rized as having many of the genotypic and phenotypic alterations commonly f ound in pancreatic tumors. METHODS. The cell line was characterized by its morphology, growth rate in monolayer culture and soft agar, tumorigenicity in nude mice, and chromosom al analysis. Furthermore, the status of p53, Ki-ras mutation and transformi ng growth factor (TGF)-beta receptor expression were determined, The charac teristics of UK Pan-1 were compared with those of other commonly used pancr eatic carcinoma cell lines. RESULTS. Quiescent UI; Pan-1 cells could be stimulated to proliferate in gr owth factor free nutrient media, indicating a growth factor independent phe notype. UK; Pan-1 cells grew in soft agar and rapidly formed turners in nud e mice. This cell line possesses a mutation at codon 12 of the c-Ki-ras-2 g ene that is commonly found in pancreatic carcinoma Fluorescence in situ hyb ridization showed that two alleles of p53 tumor suppressor gene were presen t in UK Pan-1. However, sequencing analysis revealed a mutation in one alle le at exon 8, codon 273 (G to A; Arg to His). Additional growth assays indi cated that the cell line was insensitive to negative growth regulation indu ced by exogenous TGF-beta. Molecular analysis of the TGF-beta signaling pat hway showed that UK Pan-1 did net express appreciable levels of the TGF-bet a receptor type I, II, or III mRNAs, but did express DPC4 mRNA. Karyotype a nalysis revealed an 18q21 deletion indicating a possible loss of heterozygo sity for DPC4, as well as other chromosomal deletions and rearrangements. CONCLUSIONS. This study indicates that UK Pan-1 is a highly tumorigenic cel l line possessing a molecularly complex pattern of mutations that may be us ed as a model to further the understanding of the mechanisms responsible fo r the development of pancreatic carcinoma. (C) 2000 American Cancer Society .