Establishment and characterization of four human pancreatic carcinoma cell lines. Genetic alterations in the TGFBR2 gene but not in the MADH4 gene

Cell Tissue Res. 2002 May;308(2):205-14. doi: 10.1007/s00441-001-0510-y. Epub 2002 Apr 11.

Abstract

We characterized four pancreatic carcinoma cell lines (designated SNU-213, SNU-324, SNU-410, and SNU-494) established from histopathologically varied primary or liver metastatic tumor samples of Korean patients. Three cell lines grew as adherent monolayers and one as adherent and floating cell clumps. All lines had: (1) relatively high viability; (2) an absence of mycoplasma or bacterial contamination; (3) genetic heterogeneity as assessed by DNA-fingerprinting analysis; (4) an absence of MADH4 mutation. Among the lines, three lines had mutations in codon 12 in K- ras, two lines harbored p53 mutations within the DNA-binding domain; two lines had homozygous deletions in both p16 and p15 genes; and one line had a missense mutation. Two lines (SNU-324 and SNU-410) had genetic alterations in the TGFBR2 gene: the SNU-324 line had a -1-bp or +1-bp mutation in 10-bp polydeoxyadenine repeat tracts; the SNU-410 line had a genomic deletion in this gene. Mutation analysis of mismatch repair genes demonstrated that SNU-324 has two heterozygous missense mutations in different exons of the hMLH1 gene. In addition, this line showed microsatellite instability and harbored frameshift mutations in simple repeated sequences of the coding regions of the TGFBR2, BAX, and hMSH3 genes. These defects of microsatellite instability and mismatch repair genes suggest the possibility of a new mutator phenotype for pancreatic carcinogenesis. These cell lines should be very useful for studying the biology of pancreatic carcinoma, particularly those related to mutator phenotype and genetic alterations in the TGFBR2 gene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pair Mismatch / genetics
  • Carcinoma / genetics*
  • Cell Line
  • Cloning, Molecular
  • DNA Fingerprinting
  • DNA Mutational Analysis
  • DNA Repair
  • DNA, Complementary / biosynthesis
  • DNA, Complementary / genetics
  • DNA, Complementary / isolation & purification
  • DNA, Neoplasm / biosynthesis
  • DNA, Neoplasm / genetics
  • Genes, p53 / genetics
  • Humans
  • Microsatellite Repeats
  • Pancreatic Neoplasms / genetics*
  • Phenotype
  • Reverse Transcriptase Polymerase Chain Reaction
  • Thymidine / metabolism
  • Transforming Growth Factor beta / pharmacology
  • Tumor Cells, Cultured

Substances

  • DNA, Complementary
  • DNA, Neoplasm
  • Transforming Growth Factor beta
  • Thymidine