Dept. of Immunology and Infectious Disease, Shinshu University Graduate School of Medicine.
Sci Rep. 2011;1:180. doi: 10.1038/srep00180. Epub 2011 Dec 5.
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.
虽然大多数在子宫中发现的平滑肌肿瘤是良性的，但子宫平滑肌肉瘤（LMS）是极其恶性的，具有高复发和转移率。我们之前曾报道过，LMP2 （干扰素（IFN）-γ诱导因子）纯合缺失的小鼠会自发发生子宫 LMS。IFN-γ 通路对于控制肿瘤生长和侵袭非常重要，并且与几种癌症有关。在这项研究中，对人和小鼠子宫组织的实验揭示了人子宫 LMS 中存在缺陷的 LMP2 表达，该表达可追溯到 IFN-γ 途径和 JAK-1 体细胞突变对 LMP2 转录激活的特定影响。此外，对人子宫 LMS 细胞系的分析阐明了 LMP2 在恶性肌层转化和细胞周期中的生物学意义，从而暗示 LMP2 是一种抗肿瘤候选物。LMP2 作为肿瘤抑制因子的这种作用可能会为人类子宫 LMS 带来新的治疗靶标。
