beta-Catenin alteration in cancer of the ampulla of Vater.
To investigate the contribution of beta-catenin to the development of carcinoma of the ampulla of Vater, genetic alterations of beta-catenin gene, CTNNB-1 were searched. Mutational analysis of exon3 in CTNNB-1, which encodes the serine/threonine residues for GSK-3beta phosphorylation sites, was performed on 21 cases of carcinoma of the ampulla of Vater, by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by nucleotide sequencing. We found one deleted mutation at codon 32 to approximately 65 in one case of carcinoma of the ampulla of Vater. We also analyzed subcellular localization of beta-catenin protein in all cases immunohistochemically, and confirmed its accumulation in the nucleus in four cases including in a CTNNB-1 mutated one. This is the first study to show CTNNB-1 mutation and beta-catenin expression in carcinoma of the ampulla of Vater. These results suggested that abnormal Wnt-wingless signaling and in particular beta-catenin alteration caused accumulation of beta-catenin, which might partially contribute to the development of carcinoma of the ampulla of Vater.
Kawakami
M
M
First Dept. of Surgery, Sapporo Medical University, Japan.
Kimura
Y
Y
Furuhata
T
T
Zenbutsu
H
H
Yanai
Y
Y
Mukaiya
M
M
Satoh
Y
Y
Murata
S
S
Hirata
K
K
D000368:Aged; D000369:Aged, 80 and over; D000595:Amino Acid Sequence; D014670:Ampulla of Vater / Q000378:metabolism* / Q000473:pathology; D001483:Base Sequence; D003138:Common Bile Duct Neoplasms / Q000378:metabolism* / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism*; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D005091:Exons; D006801:Humans; D007124:Immunoenzyme Techniques; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin
C495270:CTNNB1 protein, human; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D004273:DNA, Neoplasm; D009363:Neoplasm Proteins; D015534:Trans-Activators; D051176:beta Catenin