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

被引：27

作者：

Hayashi, Takuma ^{[1
]}

Horiuchi, Akiko ^{[2
]}

Sano, Kenji ^{[3
]}

Hiraoka, Nobuyoshi ^{[4
]}

Kasai, Mari ^{[5
]}

Ichimura, Tomoyuki ^{[5
]}

Sudo, Tamotsu ^{[6
]}

Tagawa, Yoh-ichi ^{[7
]}

Nishimura, Ryuichiro ^{[6
]}

Ishiko, Osamu ^{[5
]}

Kanai, Yae ^{[4
]}

Yaegashi, Nobuo ^{[8
]}

Aburatani, Hiroyuki ^{[9
]}

Shiozawa, Tanri ^{[2
]}

Konishi, Ikuo ^{[10
]}

机构：

[1] Shinshu Univ, Grad Sch Med, Dept Immunol & Infect Dis, Matsumoto, Nagano, Japan

[2] Shinshu Univ, Sch Med, Dept Obstet & Gynecol, Matsumoto, Nagano, Japan

[3] Shinshu Univ Hosp, Dept Lab Med, Matsumoto, Nagano, Japan

[4] Natl Canc Ctr, Res Inst, Div Pathol, Kashiwa, Chiba, Japan

[5] Osaka City Univ, Grad Sch Med, Dept Obstet & Gynecol, Osaka, Japan

[6] Hyogo Canc Ctr, Dept Gynecol, Kobe, Hyogo, Japan

[7] Tokyo Inst Technol, Dept Biomol Engn, Tokyo, Japan

[8] Tohoku Univ, Grad Sch Med, Dept Obstet & Gynecol, Sendai, Miyagi 980, Japan

[9] Univ Tokyo, Res Ctr Adv Sci & Technol, Canc Syst Lab, Tokyo 1138654, Japan

[10] Kyoto Univ, Grad Sch Med, Dept Obstet & Gynecol, Kyoto 6068501, Japan

来源：

SCIENTIFIC REPORTS | 2011年 / 1卷

基金：

日本科学技术振兴机构;

关键词：

NF-KAPPA-B; PROTEASOME SUBUNITS; MUTATIONAL ANALYSIS; KINASE MUTATIONS; GENE-EXPRESSION; SARCOMAS; CANCER; JAK1; OVEREXPRESSION; ACTIVATION;

D O I：

10.1038/srep00180

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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)-gamma-inducible factor, spontaneously develop uterine LMS. The IFN-gamma 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-gamma 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.

引用

页数：9

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