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

doi:10.1038/srep00180

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 language	English
Article number	180
Journal	Scientific reports
Volume	1
DOIs	https://doi.org/10.1038/srep00180
Publication status	Published - 2011
Externally published	Yes

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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, Article 180. https://doi.org/10.1038/srep00180

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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",

year = "2011",

doi = "10.1038/srep00180",

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journal = "Scientific reports",

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T1 - Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy

AU - Hayashi, Takuma

AU - Horiuchi, Akiko

AU - Sano, Kenji

AU - Hiraoka, Nobuyoshi

AU - Kasai, Mari

AU - Ichimura, Tomoyuki

AU - Sudo, Tamotsu

AU - Tagawa, Yoh Ichi

AU - Nishimura, Ryuichiro

AU - Ishiko, Osamu

AU - Kanai, Yae

AU - Yaegashi, Nobuo

AU - Aburatani, Hiroyuki

AU - Shiozawa, Tanri

AU - Konishi, Ikuo

PY - 2011

Y1 - 2011

N2 - 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.

AB - 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.

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

Abstract

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