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

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Leiomyosarcoma
Interferons
Neoplasms
Muscle Neoplasms
Therapeutics
Myometrium
Transcriptional Activation
Uterus
Smooth Muscle
Cell Cycle
Neoplasm Metastasis
Recurrence
Cell Line
Mutation
Growth

ASJC Scopus subject areas

  • General

Cite this

Hayashi, T., Horiuchi, A., Sano, K., Hiraoka, N., Kasai, M., Ichimura, 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

Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy. / Hayashi, Takuma; Horiuchi, Akiko; Sano, Kenji; Hiraoka, Nobuyoshi; Kasai, Mari; Ichimura, Tomoyuki; Sudo, Tamotsu; Tagawa, Yoh Ichi; Nishimura, Ryuichiro; Ishiko, Osamu; Kanai, Yae; Yaegashi, Nobuo; Aburatani, Hiroyuki; Shiozawa, Tanri; Konishi, Ikuo.

In: Scientific Reports, Vol. 1, 180, 2011.

Research output: Contribution to journalArticle

Hayashi, T, Horiuchi, A, Sano, K, Hiraoka, N, Kasai, M, Ichimura, T, Sudo, T, Tagawa, YI, 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, vol. 1, 180. https://doi.org/10.1038/srep00180
Hayashi, Takuma ; Horiuchi, Akiko ; Sano, Kenji ; Hiraoka, Nobuyoshi ; Kasai, Mari ; Ichimura, Tomoyuki ; Sudo, Tamotsu ; Tagawa, Yoh Ichi ; Nishimura, Ryuichiro ; Ishiko, Osamu ; Kanai, Yae ; Yaegashi, Nobuo ; Aburatani, Hiroyuki ; Shiozawa, Tanri ; Konishi, Ikuo. / Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy. In: Scientific Reports. 2011 ; Vol. 1.
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