Mutations of LKB1 gene in pancreatic ductal adenocarcinomas induced by N-nitrosobis(2-oxopropyl)amine in hamsters.

Abstract

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.

• Authors: Mami Furukawa, Ayako Yamasaki, Junichi Yoshida, Megumu Tsujino, Naoko Wakabayashi, Kanya Honoki, Toshifumi Tsujiuchi
• Journal: Anticancer research (Anticancer Res) Vol. 29 Issue 10 Pg. 4047-50 (Oct 2009) ISSN: 1791-7530 [Electronic] Greece
• PMID: 19846949 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Mutagens
• Nitrosamines
• nitrosobis(2-oxopropyl)amine
• Protein Serine-Threonine Kinases

Topics

• Animals
• Carcinoma, Pancreatic Ductal (chemically induced, enzymology, genetics)
• Cricetinae
• Female
• Mesocricetus
• Mutagens
• Nitrosamines
• Pancreatic Neoplasms (chemically induced, enzymology, genetics)
• Polymorphism, Single-Stranded Conformational
• Protein Serine-Threonine Kinases (genetics)
• Reverse Transcriptase Polymerase Chain Reaction