宫颈癌中SOCS-1表达的研究新进展

每年全球大约有38万宫颈癌新发病例,已成为现今世界女性最常见的妇科恶性肿瘤之一,高危型人类乳头瘤病毒(HPV-16、18等)是公认的宫颈癌的致病因素。研究证实HPV E7原癌基因的产物HPV E7原癌蛋白通过与抑癌蛋白p Rb结合,诱导p Rb的降解,导致宫颈上皮细胞永化生,致细胞生长增殖失控及细胞凋亡程序发生异常是HPV诱导宫颈癌发生的一个主要机制。细胞因子信号传导抑制蛋白(suppressor of cytokine signaling,SOCS)家族是由细胞产生的,可通过反馈调节来阻断细胞因子信号转导过程的一类负性调节因子,SOCS-1可抑制多种细胞因子的信号转导途径,调控体内多种免疫反应,现有研究表明SOCS-1可通过诱导E7蛋白降解来抑制HPV E7介导的异常转化。而且socs-1在癌细胞中表达明显降低,说明SOCS-1可能是抑癌基因,其失活机制主要是甲基化和杂合性缺失,所以说SOCS-1的甲基化和杂合性缺失对宫颈癌的发生、发展起着至关重要的作用,因此SOCS-1的去甲基化及打破基因沉默可能是一种潜在的治疗宫颈癌的新策略。

SOCS-1 Expression in Cervical New Progress in Research

There are about 380000 new cases of cervical cancer every year, which has become one of the most common female gynecologic malignant tumor in the world today, and the high-risk human papillomavirus (HPV-16, 1 8) is acknowledged as a causal factor in cervical carcinoma. The study confirmed that HPV proto-oncogene E7 produced HPV E7 oncogene binds to the tumor suppressor protein pRb, and degrades ipRb, resulting in cervical epithelial cells metaplasia. The important mechanism of cervical carcinoma is to induce cell proliferation out of control and apoptosis induced by HPV exception. The SOCS family is produced by the cell, and blocks a negative cytokine signal transduction regulators through the feedback regulation. SOCS-1 can inhibit signal transduction pathway of a variety of cytokines, and regulate a variety of immune responses. The current study shows that E7 protein degradation induced by SOCS-1 inhibit the abnormal transformation of the HPV mediated by E7. And SOCS-1 in cancer cells was significantly decreased, indicating that SOCS-1 may be a tumor suppressor gene, whose main mechanism is its inactivation methylation and loss of heterozygosity, so SOCS-1 methylation and loss of heterozygosity plays a vital role on the cervical cancer occurrence, Therefore, the SOCS-1 demethylation and break gene silencing may be a new strategy for the potential treatment of cervical cancer.