@article{d97e41b169614c3c942c8ed5c9e6f05a,
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.",
author = "Takuma Hayashi and Akiko Horiuchi and Kenji Sano and Nobuyoshi Hiraoka and Mari Kasai and Tomoyuki Ichimura and Tamotsu Sudo and Tagawa, {Yoh Ichi} and Ryuichiro Nishimura and Osamu Ishiko and Yae Kanai and Nobuo Yaegashi and Hiroyuki Aburatani and Tanri Shiozawa and Ikuo Konishi",
note = "Funding Information: We sincerely appreciate the donation of LMP2-deficient breeding mice and scientific cooperation of Prof. Susumu Tonegawa (Picower Institute of Learning and Memory, M.I.T). We thank Dr. Isamu Ishiwata (Ishiwata Clinic, Ibaraki, Japan) for generously providing the uterine LMS cell line and also thank Dr. Yoshi Adachi (Shinshu University, Nagano, Japan) for generously providing the uterine HeLa cell line. We also thank BEX Corporation (Tokyo, Japan) for assistance with constructing plasmid vectors. We also appreciate Mr. Trevor Ralph for critical reading the manuscript. This work was supported by grants from the Ministry of Education, Culture, Science and Technology, the Japan Science and Technology Agency, The Foundation of Takeda Medical Research, The Foundation for the Promotion of Cancer Research, Kanzawa Medical Research Foundation, and The Ichiro Kanehara Foundation.",
year = "2011",
doi = "10.1038/srep00180",
language = "English",
volume = "1",
journal = "Scientific reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
}
