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

Potential role of LMP2 as tumor-suppressor defines new targets for uterine leiomyosarcoma therapy.
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LMP2 作为肿瘤抑制剂的潜在作用定义了子宫平滑肌肉瘤治疗的新靶点。

DOI:
10.1038/srep00180
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发表时间:
2011
期刊:
影响因子:
4.6
通讯作者:
Konishi, Ikuo
Konishi, Ikuo
中科院分区:
综合性期刊3区
文献类型:
--
作者:
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

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虽然大多数子宫平滑肌肿瘤是良性的, 平滑肌肉瘤(LMS)恶性程度极高,复发率和转移率高。 我们之前报道过LMP 2纯合子缺陷的小鼠,LMP 2是一种干扰素, (IFN)-γ-诱导因子,自发发展子宫LMS。IFN-γ途径很重要 用于控制肿瘤生长和侵袭,并与几种癌症有关。在这 在一项研究中,人类和小鼠子宫组织的实验显示,LMP 2表达缺陷 在人子宫LMS中,这可追溯到IFN-γ途径和JAK-1的特异性作用 体细胞突变对LMP 2转录激活的影响。此外,分析A 人子宫LMS细胞系阐明了LMP 2在恶性肿瘤中的生物学意义, 子宫肌层转化和细胞周期,从而暗示LMP 2作为抗肿瘤 候选人LMP 2作为肿瘤抑制因子的这种作用可能会导致新的治疗靶点, 人子宫LMS。
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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