help button home button Am J Pathol Epitomics, Inc.
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Purchase Article
Right arrow View Shopping Cart
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Nicholes, K.
Right arrow Articles by French, D. M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Nicholes, K.
Right arrow Articles by French, D. M.
(American Journal of Pathology. 2002;160:2295-2307.)
© 2002 American Society for Investigative Pathology

Animal Models

A Mouse Model of Hepatocellular Carcinoma

Ectopic Expression of Fibroblast Growth Factor 19 in Skeletal Muscle of Transgenic Mice

Katrina Nicholes*, Susan Guillet*, Elizabeth Tomlinson{dagger}, Kenneth Hillan*, Barbara Wright*, Gretchen D. Frantz*, Thinh A. Pham*, Lisa Dillard-Telm*, Siao Ping Tsai{ddagger}, Jean-Philippe Stephan{ddagger}, Jeremy Stinson{dagger}, Timothy Stewart{dagger} and Dorothy M. French*

From the Departments of Pathology,*Molecular Biology,{dagger}and Assay and Automation Technology,{ddagger}Genentech Incorporated, South San Francisco, California

Abstract

Most mouse models of hepatocellular carcinoma have expressed growth factors and oncogenes under the control of a liver-specific promoter. In contrast, we describe here the formation of liver tumors in transgenic mice overexpressing human fibroblast growth factor 19 (FGF19) in skeletal muscle. FGF19 transgenic mice had elevated hepatic {alpha}-fetoprotein mRNA as early as 2 months of age, and hepatocellular carcinomas were evident by 10 months of age. Increased proliferation of pericentral hepatocytes was demonstrated by 5-bromo-2'-deoxyuridine incorporation in the FGF19 transgenic mice before tumor formation and in nontransgenic mice injected with recombinant FGF19 protein. Areas of small cell dysplasia were initially evident pericentrally, and dysplastic/neoplastic foci throughout the hepatic lobule were glutamine synthetase-positive, suggestive of a pericentral origin. Consistent with chronic activation of the Wingless/Wnt pathway, 44% of the hepatocellular tumors from FGF19 transgenic mice had nuclear staining for ß-catenin. Sequencing of the tumor DNA encoding ß-catenin revealed point mutations that resulted in amino acid substitutions. These findings suggest a previously unknown role for FGF19 in hepatocellular carcinomas.




This article has been cited by other articles:


Home page
 Cancer Res.Home page
R. Pai, D. Dunlap, J. Qing, I. Mohtashemi, K. Hotzel, and D. M. French
Inhibition of Fibroblast Growth Factor 19 Reduces Tumor Growth by Modulating {beta}-Catenin Signaling
Cancer Res., July 1, 2008; 68(13): 5086 - 5095.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
B. C. Lin, M. Wang, C. Blackmore, and L. R. Desnoyers
Liver-specific Activities of FGF19 Require Klotho beta
J. Biol. Chem., September 14, 2007; 282(37): 27277 - 27284.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. Kharitonenkov, V. J. Wroblewski, A. Koester, Y.-F. Chen, C. K. Clutinger, X. T. Tigno, B. C. Hansen, A. B. Shanafelt, and G. J. Etgen
The Metabolic State of Diabetic Monkeys Is Regulated by Fibroblast Growth Factor-21
Endocrinology, February 1, 2007; 148(2): 774 - 781.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
C. Yu, F. Wang, C. Jin, X. Huang, and W. L. McKeehan
Independent Repression of Bile Acid Synthesis and Activation of c-Jun N-terminal Kinase (JNK) by Activated Hepatocyte Fibroblast Growth Factor Receptor 4 (FGFR4) and Bile Acids
J. Biol. Chem., May 6, 2005; 280(18): 17707 - 17714.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
A. M. Strack and R. W. Myers
Modulation of Metabolic Syndrome by Fibroblast Growth Factor 19 (FGF19)?
Endocrinology, June 1, 2004; 145(6): 2591 - 2593.
[Full Text] [PDF]

Home page
 EndocrinologyHome page
L. Fu, L. M. John, S. H. Adams, X. X. Yu, E. Tomlinson, M. Renz, P. M. Williams, R. Soriano, R. Corpuz, B. Moffat, et al.
Fibroblast Growth Factor 19 Increases Metabolic Rate and Reverses Dietary and Leptin-Deficient Diabetes
Endocrinology, June 1, 2004; 145(6): 2594 - 2603.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
C. Yu, F. Wang, C. Jin, X. Huang, D. L. Miller, C. Basilico, and W. L. McKeehan
Role of Fibroblast Growth Factor Type 1 and 2 in Carbon Tetrachloride-Induced Hepatic Injury and Fibrogenesis
Am. J. Pathol., October 1, 2003; 163(4): 1653 - 1662.
[Abstract] [Full Text] [PDF]

Home page
 Genes Dev.Home page
J. A. Holt, G. Luo, A. N. Billin, J. Bisi, Y. Y. McNeill, K. F. Kozarsky, M. Donahee, D. Y. Wang, T. A. Mansfield, S. A. Kliewer, et al.
Definition of a novel growth factor-dependent signal cascade for the suppression of bile acid biosynthesis
Genes & Dev., July 1, 2003; 17(13): 1581 - 1591.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Copyright © 2002 by the American Society for Investigative Pathology.