Mutations of LKB1 gene in pancreatic ductal adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters.
To evaluate an involvement of LKB1 gene alteration during pancreatic carcinogenesis, mutations in the LKB1 gene in hamster pancreatic duct adenocarcinomas (PDAs) induced by N-nitrosobis(2-oxopropyl)amine (BOP) were investigated. Female Syrian golden hamsters received 30 mg/kg of BOP followed by repeated exposure to an augmentation pressure regimen consisting of a choline-deficient diet combined with DL-ethionine then L-methionine and a further administration of 20 mg/kg BOP. A total of 10 PDAs obtained 10 weeks after beginning the experiment were examined for mutations using reverse transcription (RT)-polymerase chain reaction (PCR)-single-strand conformation polymorphism (SSCP) analysis. Mutations were detected in 3 out of the 10 PDAs (30.0%). Sequence analysis revealed the identity of these mutations to be a CCC to CCT (Pro to Pro) transition at codon 221, a CCG to CAG (Pro to Gln) transversion at codon 324 and a GAC to GGC (Asp to Gly) transition at codon 343. The LKB1 gene may be involved in the development of PDAs induced by BOP in hamsters.
Furukawa
Mami
M
Laboratory of Cancer Biology and Bioinformatics, Department of Life Science, Faculty of Science and Engineering, Kinki University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Yamasaki
Ayako
A
Yoshida
Junichi
J
Tsujino
Megumu
M
Wakabayashi
Naoko
N
Honoki
Kanya
K
Tsujiuchi
Toshifumi
T
D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D006224:Cricetinae; D005260:Female; D008647:Mesocricetus; D009153:Mutagens; D009602:Nitrosamines; D010190:Pancreatic Neoplasms / Q000139:chemically induced* / Q000201:enzymology / Q000235:genetics*; D018807:Polymorphism, Single-Stranded Conformational; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009153:Mutagens; D009602:Nitrosamines; C013622:nitrosobis(2-oxopropyl)amine; D017346:Protein Serine-Threonine Kinases