title: Characterization of a newly established human pancreatic carcinoma cell line, UK Pan-1.
abstract: BACKGROUND
  A highly tumorigenic cell line designated as UK Pan-1 was established in a surgically removed human pancreatic adenocarcinoma and characterized as having many of the genotypic and phenotypic alterations commonly found 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 chromosomal analysis. Furthermore, the status of p53, Ki-ras mutation and transforming growth factor (TGF)-/receptor expression were determined. The characteristics of UK Pan-1 were compared with those of other commonly used pancreatic carcinoma cell lines.
  
  
  RESULTS
  Quiescent UK Pan-1 cells could be stimulated to proliferate in growth factor free nutrient media, indicating a growth factor independent phenotype. UK Pan- 1 cells grew in soft agar and rapidly formed tumors in nude mice. This cell line possesses a mutation at codon 12 of the c-Ki-ras-2 gene that is commonly found in pancreatic carcinoma. Fluorescence in situ hybridization showed that two alleles of p53 tumor suppressor gene were present in UK Pan-1. However, sequencing analysis revealed a mutation in one allele at exon 8, codon 273 (G to A; Arg to His). Additional growth assays indicated that the cell line was insensitive to negative growth regulation induced by exogenous TGF-beta. Molecular analysis of the TGF-beta signaling pathway showed that UK Pan-1 did not express appreciable levels of the TGF-beta receptor type I, II, or III mRNAs, but did express DPC4 mRNA. Karyotype analysis revealed an 18q21 deletion indicating a possible loss of heterozygosity for DPC4, as well as other chromosomal deletions and rearrangements.
  
  
  CONCLUSIONS
  This study indicates that UK Pan-1 is a highly tumorigenic cell line possessing a molecularly complex pattern of mutations that may be used as a model to further the understanding of the mechanisms responsible for the development of pancreatic carcinoma.
authors.affiliation: Department of Surgery, University of Texas Health Science Center, San Antonio 78284-7842, USA.
authors.forename: K D
authors.initials: KD
authors.lastname: Fralix
authors.forename: M M
authors.initials: MM
authors.lastname: Ahmed
authors.forename: C
authors.initials: C
authors.lastname: Mattingly
authors.forename: C
authors.initials: C
authors.lastname: Swiderski
authors.forename: P C
authors.initials: PC
authors.lastname: McGrath
authors.forename: K
authors.initials: K
authors.lastname: Venkatasubbarao
authors.forename: N
authors.initials: N
authors.lastname: Kamada
authors.forename: M
authors.initials: M
authors.lastname: Mohiuddin
authors.forename: W E
authors.initials: WE
authors.lastname: Strodel
authors.forename: J W
authors.initials: JW
authors.lastname: Freeman
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D000483:Alleles; D000818:Animals; D002455:Cell Division; D003062:Codon / Q000235:genetics; D003470:Culture Media; D004268:DNA-Binding Proteins / Q000235:genetics; D005091:Exons / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D005838:Genotype; D006801:Humans; D019656:Loss of Heterozygosity / Q000235:genetics; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009154:Mutation / Q000235:genetics; D009368:Neoplasm Transplantation; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000473:pathology*; D010641:Phenotype; D017354:Point Mutation / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D051901:Smad4 Protein; D015534:Trans-Activators / Q000235:genetics; D016212:Transforming Growth Factor beta / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D003062:Codon; D003470:Culture Media; D004268:DNA-Binding Proteins; D018125:Receptors, Transforming Growth Factor beta; C497796:SMAD4 protein, human; D051901:Smad4 Protein; C490810:Smad4 protein, mouse; D015534:Trans-Activators; D016212:Transforming Growth Factor beta