Constitutive expression of ErbB-2 in gallbladder epithelium results in development of adenocarcinoma

Overexpression of ErbB-2 in the basal layer of biliary tract epithelium led to the development of gallbladder adenocarcinoma in 100% of transgenic mice by 3 months of age. In addition, tumors developed in other parts of the biliary tree (e.g., cholangiocarcinoma). Adenocarcinoma of the gallbladder a...

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Bibliographic Details
Published in:Cancer research (Chicago, Ill.) Ill.), 2001-10, Vol.61 (19), p.6971-6976
Main Authors: KIGUCHI, Kaoru, CARBAJAL, Steve, CHAN, Keith, BELTRAN, Linda, RUFFINO, Lynnsie, SHEN, Jianjun, MATSUMOTO, Takashi, YOSHIMI, Naoki, DIGIOVANNI, John
Format: Article
Language:English
Subjects:
Adenocarcinoma - genetics
Adenocarcinoma - metabolism
Animals
Biological and medical sciences
Cell physiology
Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes
Cyclooxygenase 2
Epithelium - metabolism
Epithelium - pathology
Epithelium - physiology
erbB-2 gene
Female
Fluorescent Antibody Technique, Indirect
Fundamental and applied biological sciences. Psychology
Gallbladder - metabolism
Gallbladder - pathology
Gallbladder - physiology
Gallbladder Neoplasms - genetics
Gallbladder Neoplasms - metabolism
Gene Expression
Genes, p53 - genetics
Genes, ras - genetics
Isoenzymes - biosynthesis
Isoenzymes - genetics
Male
Mice
Mice, Transgenic
Mitogen-Activated Protein Kinases - metabolism
Molecular and cellular biology
Mutation
Phosphatidylinositol 3-Kinases - metabolism
Prostaglandin-Endoperoxide Synthases - biosynthesis
Prostaglandin-Endoperoxide Synthases - genetics
Receptor, ErbB-2 - blood
Receptor, ErbB-2 - genetics
Receptor, ErbB-2 - physiology
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - biosynthesis
RNA, Messenger - genetics
Signal Transduction - physiology
src-Family Kinases - metabolism
Transgenes
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Description
Summary:Overexpression of ErbB-2 in the basal layer of biliary tract epithelium led to the development of gallbladder adenocarcinoma in 100% of transgenic mice by 3 months of age. In addition, tumors developed in other parts of the biliary tree (e.g., cholangiocarcinoma). Adenocarcinoma of the gallbladder appeared to arise via a stepwise process involving hyperplasia, adenoma formation, and then adenocarcinoma formation. Increased ErbB-2/epidermal growth factor receptor heterodimer formation, activation of mitogen-activated protein kinase, and up-regulation of cyclooxygenase-2 levels (mRNA and protein) were observed in gallbladder epithelium of these mice. These mice represent a unique new animal model for studying biliary tract carcinogenesis.
ISSN:0008-5472
1538-7445