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 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.
Kiguchi
K
K
The University of Texas, M. D. Anderson Cancer Center, Science Park Research Division, Smithville, Texas 78957, USA.
Carbajal
S
S
Chan
K
K
Beltrán
L
L
Ruffino
L
L
Shen
J
J
Matsumoto
T
T
Yoshimi
N
N
DiGiovanni
J
J
D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2; D004848:Epithelium / Q000378:metabolism / Q000473:pathology / Q000502:physiology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D005704:Gallbladder / Q000378:metabolism* / Q000473:pathology / Q000502:physiology; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D007527:Isoenzymes / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000097:blood* / Q000235:genetics / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D019076:Transgenes; D019061:src-Family Kinases / Q000378:metabolism
D051546:Cyclooxygenase 2; D007527:Isoenzymes; D020928:Mitogen-Activated Protein Kinases; D019869:Phosphatidylinositol 3-Kinases; D011451:Prostaglandin-Endoperoxide Synthases; D012333:RNA, Messenger; D018719:Erb-b2 Receptor Tyrosine Kinases; D019061:src-Family Kinases