背景:90kDa/泛素样具有PHD和RING指域1(ICBP90/UHRF1)和Np95样无名指蛋白(NIRF)的反向CCAAT盒结合蛋白的蛋白表达发生了改变,属于泛素样具有PHD和RING指域(UHRF)家族,与肿瘤恶性肿瘤和各种癌症的进展有关。为了确定NIRF和ICBP90在子宫内膜肿瘤发生中的作用,我们评估了子宫内膜癌中ICBP90和NIRF的表达水平.PTEN表达的分子改变也是子宫内膜癌发生的重要事件。因此,我们研究了ICBP90和PTEN表达之间的关系.
方法:我们使用蛋白质印迹法进行NIRF,ICBP90和PTEN表达,NIRF基因突变分析,免疫组化染色检测NIRF和ICBP90的表达。对于免疫组织化学染色,我们检查了不典型的子宫内膜增生,子宫内膜癌,和非癌症样本。
结果:我们的数据显示,与正常子宫内膜相比,非典型子宫内膜增生和子宫内膜癌中NIRF的表达降低和ICBP90的过表达。NIRF表达的降低与组织学分级显着相关。ICBP90高表达,尤其是在癌巢的周边边缘。子宫内膜癌细胞系的蛋白质印迹分析提到了ICBP90与磷酸酶和张力蛋白同源物(PTEN)表达之间的相反相关性。
结论:我们的研究结果表明,持续过度表达的ICBP90可能有助于抑制PTEN表达,这是子宫内膜癌变过程中常见的重要事件。我们认为NIRF表达降低和ICBP90过表达是子宫内膜癌变的早期事件;因此ICBP90可能作为该疾病的治疗靶标。
BACKGROUND: The altered protein expression of inverted CCAAT box-binding protein of 90 kDa/ubiquitin-like with PHD and RING finger domains 1 (
ICBP90/UHRF1) and Np95-like ring finger protein (NIRF)/UHRF2, which belong to the ubiquitin-like with PHD and RING finger domains (UHRF) family, is linked to tumor malignancy and the progression of various cancers. To determine the role of NIRF and
ICBP90 in endometrial tumorigenesis, we evaluated
ICBP90 and NIRF expression levels in endometrial cancers. Also molecular alterations of phosphatase and tensin homolog (PTEN) expression are the important event for endometrial carcinogenesis; therefore, we investigated the involvement between ICBP90 and PTEN expression.
METHODS: We used Western blot for NIRF, ICBP90, and PTEN expression, mutation analysis of NIRF gene, and immunohistochemical staining for the expression of NIRF and
ICBP90. For immunohistochemical staining, we examined atypical endometrial hyperplasia, endometrial cancers, and noncancerous samples.
RESULTS: Our data showed that the reduced expression of NIRF and overexpression of ICBP90 occurred in atypical endometrial hyperplasia and endometrial cancer compared to the normal endometrium. The decrease in NIRF expression was significantly correlated with histological grade. Expression of
ICBP90 was high, especially in the peripheral margin of a cancer nest. Western blot analysis of endometrial cancer cell lines referred an opposite correlation between ICBP90 and PTEN expression.
CONCLUSIONS: Our findings suggested that continually overexpressed ICBP90 may contribute to the inhibition of PTEN expression, which is a frequent and important event in endometrial carcinogenesis. We propose that the reduced NIRF expression and ICBP90 overexpression is an early event in endometrial carcinogenesis; thus
ICBP90 may be useful as a therapeutic target in this disease.