Department of Radiation Oncology, Chungbuk National University College of Medicine, Cheongju, Republic of Korea.
J Cell Physiol. 2011 Jun;226(6):1564-72. doi: 10.1002/jcp.22486.
The high incidence and fatality rate of uterine cervical cancer warrant effective diagnostic and therapeutic target identification for this disease. Here, we have found a novel oncoprotein FTS (Fused Toes Homolog), which is involved in cervical cancer pathogenesis. Immunohistochemical analysis of human cervical biopsy samples revealed that the expression of FTS is absent in normal cervical epithelium but progressively overexpressed in human cervical intraneoplastic lesions (CIN-I to CIN-III), this characteristic phenomenon put this protein, a potential diagnostic marker for the screening of early neoplastic changes of cervix. Using FTS-specific small hairpin RNA (shRNA) in cervical cancer cells, we determined a specific role for FTS protein in, cervical neoplasia. Targeted stable knock down of FTS in HeLa cells led to the growth inhibition, cell-cycle arrest, and apoptosis with concurrent increase in p21 protein. FTS effectively represses the p21 mRNA expression in dual luciferase assay which indicates that p21 is transcriptionally regulated by this oncoprotein which in turn affect the regular cell-cycle process and its components. Consistent with this we found a reciprocal association between these proteins in early cervical neoplastic tissues. These data unraveled the involvement of new oncoprotein FTS in cervical cancer which plays a central role in carcinogenesis. Targeted inhibition of FTS lead to the shutdown of key elemental characteristics of cervical cancer and could lead to an effective therapeutic strategy for cervical cancer.
宫颈癌的高发病率和死亡率使得我们有必要寻找有效的诊断和治疗靶点。在这里，我们发现了一种新的癌蛋白 FTS（融合趾同源物），它参与了宫颈癌的发病机制。对人宫颈活检样本的免疫组织化学分析表明，FTS 的表达在正常宫颈上皮中不存在，但在人宫颈内瘤样病变（CIN-I 至 CIN-III）中逐渐过表达，这种特征性现象使该蛋白成为筛查宫颈早期肿瘤变化的潜在诊断标志物。我们使用针对 FTS 的特异性短发夹 RNA（shRNA）在宫颈癌细胞中确定了 FTS 蛋白在宫颈癌发生中的特定作用。FTS 在 HeLa 细胞中的靶向稳定敲低导致生长抑制、细胞周期停滞和凋亡，同时 p21 蛋白增加。FTS 在双荧光素酶测定中有效抑制 p21 mRNA 的表达，表明 p21 受这种癌蛋白的转录调控，进而影响正常的细胞周期过程及其成分。与此一致，我们在早期宫颈肿瘤组织中发现了这些蛋白之间的相互关联。这些数据揭示了新的癌蛋白 FTS 参与宫颈癌的发生，它在致癌作用中起着核心作用。FTS 的靶向抑制导致宫颈癌的关键元素特征失活，可能为宫颈癌的治疗提供有效的策略。
