title: Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy.
abstract: Although the majority of smooth muscle neoplasms found in the uterus are benign, uterine leiomyosarcoma (LMS) is extremely malignant, with high rates of recurrence and metastasis. We earlier reported that mice with a homozygous deficiency for LMP2, an interferon (IFN)-γ-inducible factor, spontaneously develop uterine LMS. The IFN-γ pathway is important for control of tumor growth and invasion and has been implicated in several cancers. In this study, experiments with human and mouse uterine tissues revealed a defective LMP2 expression in human uterine LMS that was traced to the IFN-γ pathway and the specific effect of JAK-1 somatic mutations on the LMP2 transcriptional activation. Furthermore, analysis of a human uterine LMS cell line clarified the biological significance of LMP2 in malignant myometrium transformation and cell cycle, thus implicating LMP2 as an anti-tumorigenic candidate. This role of LMP2 as a tumor suppressor may lead to new therapeutic targets in human uterine LMS.
authors.affiliation: Dept. of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine. 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: Mari
authors.initials: M
authors.lastname: Kasai
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Ichimura
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Sudo
authors.forename: Yoh-Ichi
authors.initials: Y
authors.lastname: Tagawa
authors.forename: Ryuichiro
authors.initials: R
authors.lastname: Nishimura
authors.forename: Osamu
authors.initials: O
authors.lastname: Ishiko
authors.forename: Yae
authors.initials: Y
authors.lastname: Kanai
authors.forename: Nobuo
authors.initials: N
authors.lastname: Yaegashi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Aburatani
authors.forename: Tanri
authors.initials: T
authors.lastname: Shiozawa
authors.forename: Ikuo
authors.initials: I
authors.lastname: Konishi
mesh_terms: D000818:Animals; D003546:Cysteine Endopeptidases / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D007890:Leiomyosarcoma / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D009215:Myometrium / Q000378:metabolism; D015533:Transcriptional Activation; D014162:Transfection; D014594:Uterine Neoplasms / Q000235:genetics / Q000378:metabolism*; D014599:Uterus / Q000378:metabolism
chemical_list: C071313:LMP-2 protein; D007371:Interferon-gamma; D003546:Cysteine Endopeptidases