Loss of p16/Ink4a drives high frequency of rhabdomyosarcoma in a rat model of Duchenne muscular dystrophy
-
- TERAMOTO Naomi
- Laboratory of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
-
- IKEDA Masanari
- Laboratory of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
-
- SUGIHARA Hidetoshi
- Laboratory of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
-
- SHIGA Takanori
- Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
-
- MATSUWAKI Takashi
- Laboratory of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
-
- NISHIHARA Masugi
- Laboratory of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
-
- UCHIDA Kazuyuki
- Laboratory of Veterinary Pathology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
-
- YAMANOUCHI Keitaro
- Laboratory of Veterinary Physiology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo 113-8657, Japan
この論文をさがす
説明
<p>Rhabdomyosarcoma (RMS) is an aggressive type of soft tissue sarcoma, and pleomorphic RMS is a rare subtype of RMS found in adult. p16 is a tumor suppressor which inhibits cell cycle. In human RMS, p16 gene is frequently deleted, but p16-null mice do not develop RMS. We reported that genetic ablation of p16 by the crossbreeding of p16 knock-out rats (p16-KO rats) improved the dystrophic phenotype of a rat model of Duchenne muscular dystrophy (Dmd-KO rats). However, p16/Dmd double knock-out rats (dKO rats) unexpectedly developed sarcoma. In the present study, we raised p16-KO, Dmd-KO, and dKO rats until 11 months of age. Twelve out of 22 dKO rats developed pleomorphic RMS after 9 months of age, while none of p16-KO rats and Dmd-KO rats developed tumor. The neoplasms were connected to skeletal muscle tissue with indistinct borders and characterized by diffuse proliferation of pleomorphic cells which had eosinophilic cytoplasm and atypical nuclei with anisokaryosis. For almost all cases, the tumor cells immunohistochemically expressed myogenic markers including desmin, MyoD, and myogenin. The single cell cloning from tumor primary cells gained 20 individual Pax7-negative MyoD-positive RMS cell clones. Our results demonstrated that double knock-out of p16 and dystrophin in rats leads to the development of pleomorphic RMS, providing an animal model that may be useful to study the developmental mechanism of pleomorphic RMS.</p>
収録刊行物
-
- Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｖｅｔｅｒｉｎａｒｙ Ｍｅｄｉｃａｌ Ｓｃｉｅｎｃｅ
-
Ｔｈｅ Ｊｏｕｒｎａｌ ｏｆ Ｖｅｔｅｒｉｎａｒｙ Ｍｅｄｉｃａｌ Ｓｃｉｅｎｃｅ 83 (9), 1416-1424, 2021
公益社団法人 日本獣医学会
