The role of TSC403/DC-Lamp gene in cervical carcinogenesis

为了阐明TSC403/DC-Lamp基因在宫颈癌中的作用，特别是在宫颈癌转移中的作用，我们设计了以下实验。定量RT-PCR显示TSC403/DC-Lamp在正常宫颈组织中不表达，而在宫颈癌组织中高表达。此外，TSC403/DC-Lamp的高表达水平与I/II期宫颈癌患者的总生存期显著相关。提示TSC403/DC-Lamp的表达可作为判断宫颈癌预后的分子标志物。我们还将TSC403/DC-LAMP表达载体导入人宫颈癌细胞系TCS。体外侵袭实验显示，TSC403/DC-LAMP过表达的TCS细胞的迁移能力明显高于对照TCS细胞。体内转移实验显示，TSC403/DC-LAMP过表达的TSC细胞的远处转移显著高于对照TCS细胞。提示TSC403/DC-Lamp的表达与宫颈癌的侵袭转移密切相关。此外，我们还鉴定了TSC403基因的启动子结构域，以阐明TSC403基因过表达的分子机制。为了检测TSC403/DC-Lamp蛋白在细胞中的定位，我们构建了GFP标记的载体，并将其导入宫颈癌细胞。TSC403/DC-Lamp蛋白在宫颈癌细胞的细胞膜上特异表达。

In order to clarify the role of the TSC403/DC-Lamp gene in uterine cervical cancer, especially concerning metastasis, following experiments were designed. Quantitative RT-PCR showed TSC403/DC-Lamp mRNA expression was not detectable in normal uterine cervical tissue but highly expressed in uterine cervical cancer. In addition, high expression level of TSC403/DC-Lamp was significantly correlated with the overall survival of patients with stage I/II cervical cancer. These indicate that TSC403/DC-Lamp expression may be a prognostic molecule marker for cervical cancer. We also transfected a TSC403/DC-LAMP expression vector into a human uterine cervical cancer cell line, TCS. In vitro invasion assay showed the migration of TSC403/DC-LAMP-overexpressing TCS cells was significantly higher than in control TCS cells. In vivo metastasis assay demonstrated distant metastasis was significantly higher in TSC403/DC-lamp-overexpressing TSC cells than in control TCS cells. These results indicate that expression of TSC403/DC-Lamp associates with invasion and metastasis in uterine cervix cancer. Furthermore, we identified a promoter domain of a TSC403 gene to elucidate molecule mechanism of overexpression of a TSC403 gene. To examine the localization of TSC403/DC-Lamp protein in the cell, we have established the GFP-tagged vector and transfected to cervical cancer cell. TSC403/DC-Lamp protein was shown to be expressed specifically on a cell membrane in uterine cervix cancer cell.