The expression control and biofunctional analysis of RCAS1

RCAS1的表达调控及生物功能分析

• 批准号: 14571568
• 负责人: SONODA Kenzo
• 金额: $ 2.24万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2003
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14571568/
• 关键词: Gynecologic oncology; Invasion; Metastasis; Anoptosis; Tumor stroma; Lymphocyte; Fibroblast; Molecular biology; 腫瘍間質

(1) RCAS1 expression in uterine endometrial cancer : Immunohistochemical analysis, using 147 patients' samples, showed that overexpression of RCAS1 was significantly correlated with age at surgery, stage, extent of myornetrial invasion, and positive peritoneal cytologic results. Multivariate analysis revealed that RCAS1 expression and metastasis were clinically significant prognostic factors for overall survival. These findings indicated that analysis for RCAS1 expression can provide crucial information about the clinical behavior of uterine endometrial cancer, which may be valuable for management of patients with this disease.(2) RCAS1 induces microenvironmental change in uterine cancer : (1)RCAS1 associated with tumor size. (2)RCAS1 related with the number of lymphocyte apoptosis in metastatic lymph nodes, (3)RCAS1 expression induced reduction of vimentin positive tumor stromal cells, (4)RCAS1 was correlated with tumor VEOF expression and stromal microvessel density. Accumulating these data, RCAS1 might play a pivotal role in tumor invasion and metastasis. (5)Serum RCAS1 level was measured by ELISA analysis. RCAS1 level was significantly higher in uterine cancer patients than in healthy donors. RCAS1 level changed in response to clinical inanifestation increased in recurrence, and decreased after effective treatments. Moreover, serum RCAS1 induced apoptosis of putative receptor-expressing K562 cells in vitro. These data indicated that RCAS1 might be a novel biomarker in management of uterine cancer patients.(3) Several basic studies are now under investigation : (1)The analysis of phenotype and signal transduction mechanism of RCAS1, by using truncation mutant transfected cells, and (2)Isolation of protease which induces proteolytic processing of RCAS1.

(1)RCAS 1在子宫内膜癌中的表达：使用147例患者样本的免疫组织化学分析显示，RCAS 1的过表达与手术时的年龄、分期、肌层浸润程度和阳性腹膜细胞学结果显著相关。多因素分析显示，RCAS 1表达和转移是影响总生存率的临床显著预后因素。这些发现表明，RCAS 1表达的分析可以提供关于子宫内膜癌的临床行为的重要信息，这可能对患有这种疾病的患者的管理有价值。(2)RCAS 1诱导子宫癌微环境改变：（1）RCAS 1与肿瘤大小相关。（2）RCAS 1与转移淋巴结中淋巴细胞凋亡数有关;（3）RCAS 1表达可导致Vimentin阳性肿瘤间质细胞减少;（4）RCAS 1与肿瘤VEOF表达及间质微血管密度有关。RCAS 1可能在肿瘤的侵袭和转移过程中发挥重要作用。（5）ELISA法检测血清RCAS 1水平。RCAS 1水平在子宫癌患者中显著高于健康供体。RCAS 1水平随临床表现的改变而变化，复发时升高，有效治疗后下降。此外，血清RCAS 1在体外诱导推定的受体表达的K562细胞凋亡。这些数据表明，RCAS 1可能是一种新的生物标志物在子宫癌患者的管理。(3)目前正在进行的基础性研究有：（1）利用截短突变体转染细胞，分析RCAS 1的表型和信号转导机制;（2）分离诱导RCAS 1蛋白水解加工的蛋白酶。

项目成果

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