Research articles

Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma

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  • 1.Department of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan;Promoting Business using Advanced Technology, Japan Science and Technology Agency (JST), Kawaguchi-shi, Saitama 332-0012, Japan; 2.Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Nagano 390-8621, Japan; 3.Department of Laboratory Medicine, Shinshu University Hospital, Matsumoto, Nagano 390-8621, Japan; 4.Pathology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan; 5.Picower Institution and Department of Biology, Massachusetts Institute of Technology, Cambridge,?Massachusetts?02139, USA; 6.Department of Obstetrics and Gynecology, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto 606-8501, Japan;

Published date: 01 Aug 2010

Abstract

Uterine tumors are the most common type of gynecologic neoplasm. Uterine leiomyosarcoma (LMS) is rare, accounting for 2% to 5% of tumors of the uterine body. Uterine LMS develops more often in the muscle tissue layer of the uterine body than in the uterine cervix. The development of gynecologic tumors is often correlated with female hormone secretion; however, the development of uterine LMS is not substantially correlated with hormonal conditions, and the risk factors are not yet known. Radiographic evaluation combined with PET/CT can be useless in the diagnosis and surveillance of uterine LMS. Importantly, a diagnostic biomarker, which distinguishes malignant LMS and benign tumor leiomyoma (LMA) is yet to be established. Accordingly, it is necessary to analyze risk factors associated with uterine LMS in order to establish a method of treatment. LMP2-deficient mice spontaneously develop uterine LMS, with a disease prevalence of ~40% by 14 months of age. It is therefore of interest whether human uterine LMS shows a loss of LMP2 expression. We found LMP2 expression is absent in human LMS, but present in human LMA. Therefore, defective LMP2 expression may be one of the risk factors for LMS. LMP2 is potentially a diagnostic biomarker for uterine LMS, and gene therapy with LMP2-encording DNA may be a new therapeutic approach.

Cite this article

Takuma Hayashi, Akiko Horiuchi, Tanri Shiozawa, Kenji Sano, Nobuyoshi Hiraoka, Yae Kanai, Susumu Tonegawa, Ikuo Konishi, . Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma[J]. Protein & Cell, 2010 , 1(8) : 711 -717 . DOI: 10.1007/s13238-010-0095-x

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