Overactive beta-catenin signaling causes testicular sertoli cell tumor development in the mouse.
Overactive WNT/beta-catenin signaling has been found in many forms of cancer in human patients. Mouse models with mutations in different components of the WNT/beta-catenin signaling pathway have been generated to mimic tumorigenesis in humans. Mice with mutations that result in overactive WNT/beta-catenin signaling developed tumors in some tissues, such as digestive tract, skin, and ovary, but they failed to develop tumors in other tissues, such as mammary gland, liver, kidney, and primordial germ cells. To investigate whether overactive beta-catenin signaling is capable of inducing Sertoli cell tumorigenesis in testes, we generated Ctnnb1(tm1Mmt/+);Tg(AMH-cre)1Flor male mice that express a constitutively active form of beta-catenin specifically in Sertoli cells. No tumors were observed at 4 mo of age, but 70% of the mutant males developed Sertoli cell tumors at 8 mo of age. At 1 yr of age, more than 90% of the mutant males developed tumors. No instances of extratesticular spread of the tumors were found in the mutant mice. These studies show a causal link between overactive WNT/beta-catenin signaling and Sertoli cell tumor development and provide a novel mouse model for the study of Sertoli cell tumor biology.
Chang
Hao
H
Program in Genes and Development, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.
Guillou
Florian
F
Taketo
Makoto M
MM
Behringer
Richard R
RR
D000818:Animals; D049109:Cell Proliferation; D005455:Fluorescent Antibody Technique; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D012707:Sertoli Cell Tumor / Q000235:genetics / Q000378:metabolism*; D012708:Sertoli Cells / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D013194:Staining and Labeling; D013736:Testicular Neoplasms / Q000235:genetics / Q000378:metabolism*; D013737:Testis / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D051176:beta Catenin