title: Mice-lacking LMP2, immuno-proteasome subunit, as an animal model of spontaneous uterine leiomyosarcoma.
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.
authors.affiliation: Department of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine, Matsumoto, Nagano 390-8621, Japan. takumah@shinshu-u.ac.jp
authors.forename: Takuma
authors.initials: T
authors.lastname: Hayashi
authors.forename: Akiko
authors.initials: A
authors.lastname: Horiuchi
authors.forename: Kenji
authors.initials: K
authors.lastname: Sano
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hiraoka
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Tanri
authors.initials: T
authors.lastname: Shiozawa
authors.forename: Susumu
authors.initials: S
authors.lastname: Tonegawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000096:biosynthesis / Q000235:genetics; D003546:Cysteine Endopeptidases / Q000096:biosynthesis / Q000235:genetics*; D015536:Down-Regulation; D005260:Female; D017353:Gene Deletion; D006801:Humans; D050856:Interferon Regulatory Factor-1 / Q000096:biosynthesis / Q000235:genetics; D007889:Leiomyoma / Q000378:metabolism; D007890:Leiomyosarcoma / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D014594:Uterine Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D050856:Interferon Regulatory Factor-1; C071313:LMP-2 protein; D003546:Cysteine Endopeptidases; D046988:Proteasome Endopeptidase Complex