Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy

Takuma Hayashi, Akiko Horiuchi, Kenji Sano, Nobuyoshi Hiraoka, Mari Kasai, Tomoyuki Ichimura, Tamotsu Sudo, Yoh Ichi Tagawa, Ryuichiro Nishimura, Osamu Ishiko, Yae Kanai, Nobuo Yaegashi, Hiroyuki Aburatani, Tanri Shiozawa, Ikuo Konishi

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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.

Original languageEnglish
Article number180
JournalScientific reports
Volume1
DOIs
Publication statusPublished - 2011
Externally publishedYes

ASJC Scopus subject areas

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    Hayashi, T., Horiuchi, A., Sano, K., Hiraoka, N., Kasai, M., Ichimura, T., Sudo, T., Tagawa, Y. I., Nishimura, R., Ishiko, O., Kanai, Y., Yaegashi, N., Aburatani, H., Shiozawa, T., & Konishi, I. (2011). Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy. Scientific reports, 1, [180]. https://doi.org/10.1038/srep00180