Establishment and characterization of four human pancreatic carcinoma cell lines. Genetic alterations in the TGFBR2 gene but not in the MADH4 gene.
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.
Ku
Ja-Lok
JL
Laboratory of Cell Biology, Korean Cell Line Bank, Cancer Research Center and Cancer Research Institute, Seoul National University College of Medicine, 28 Yongon-dong, Chongno-gu, Seoul, 110-744, Korea.
Yoon
Kyong-Ah
KA
Kim
Woo-Ho
WH
Jang
Young
Y
Suh
Kyung-Suk
KS
Kim
Sun-Whe
SW
Park
Yong-Hyun
YH
Park
Jae-Gahb
JG
D020137:Base Pair Mismatch / Q000235:genetics; D002277:Carcinoma / Q000235:genetics*; D002460:Cell Line; D003001:Cloning, Molecular; D016172:DNA Fingerprinting; D004252:DNA Mutational Analysis; D004260:DNA Repair; D018076:DNA, Complementary / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification; D004273:DNA, Neoplasm / Q000096:biosynthesis / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D018895:Microsatellite Repeats; D010190:Pancreatic Neoplasms / Q000235:genetics*; D010641:Phenotype; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013936:Thymidine / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D018076:DNA, Complementary; D004273:DNA, Neoplasm; D016212:Transforming Growth Factor beta; D013936:Thymidine