STUDY OF TELOMERASE ACTIVITY AND EXPRESSION OF THE CATALYTIC SUBUNIT ASSOCIATED WITH THIS GENE IN HUMAN UROLOGICAL CANCER.

研究人类泌尿癌中端粒酶活性和与该基因相关的催化亚基的表达。

• 批准号: 09671645
• 负责人: FUJIOKA Tomoaki
• 金额: $ 1.86万
• 依托单位: IWATE MEDICAL UNIVERSITY SCHOOL OF MEDICINE,DEPARTMENT OF UROLOGY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09671645/
• 关键词: Telomerase activity; Telomerase-subunit; TRAP assay; RT-PCR method; renal cell carcinoma; bladder cancer; oncogene; tumor-maker; テロメラーゼ; 分子生物学; テロメラーゼ・サブセット; hEST2; hTRT; TLP1; TPI; 膀胱正常組織; 集団検診; 尿剥離細胞; TRAP Assay; 前立腺癌; テロメア長; サザンブロツ

Teromerase is the ribonucleoprotein enzyme associated with the immortalization and oncogenesis of cancer cells. Telomerase activity was examined in 47 RCCs using PCR-based telomeric repeat amplification protocol (TRAP) assay. Among 30 RCCs, 18 samples(60%) displayed the activity, white none of the normal tissues exhibited the activity. Subdivision of the tumors according to telomerase activity did not reveal any obvious difference in distribitution of tumor size, stage, histocytological subtype, or DNA-ploidy. However, statistically significant relationship between the frequency of telomerase-positive activity and serum lAP levels or tumor grade was foumd, respectively (p<0.05). These results indicate that telomerase activity may be an important factor for' evaluating the malignancy potential of RCC, rather than for detecting malignancy of the kidney.Although TRAP assay is a highly sensitivity method, it has been reported that Taq inhibitor and other factors in method might cause false results during PCR amplification. Recently, three new major components of telomerase genes which are hTR, TLP1/TPI, and hEST2/hTRT has been cloned. In 27 human urinary bladder cancers, expression of hEST2/hTRT and TLP1/TPI was studied by using revel-se transcriptase-polymerase chain reaction (RT-PCR) method. In all 27 cancers (100%), hEST2/hTRT expression was detected, while TLP1/TPL was displayed in 25 of 27 speciniens(92%). Five normal bladder tissues showed no expression of hEST2/hTRT, but 3 of 5 tisses (60%) did TLPl/TP1 expression. These results indicated that RT-PCR for detecting expression of hEST2/hTRP gene may be a powerful method for the mass screening or diagnosis of urinary bladder.

端粒酶是与癌细胞的永生化和肿瘤发生相关的核糖核蛋白酶。应用聚合酶链反应（PCR）端粒重复序列扩增法（TRAP）检测47例RCC中端粒酶活性。30例肾细胞癌中18例（60%）有活性，正常组织中无一例（白色）有活性。根据端粒酶活性对肿瘤进行的细分在肿瘤大小、分期、组织细胞学亚型或DNA倍体的分布上没有发现任何明显的差异。端粒酶阳性率与血清IAP水平及肿瘤分级相关（P<0.05）。TRAP法是一种敏感性较高的检测肾癌的方法，但也有报道称该方法中的Taq酶抑制剂等因素可能会导致PCR扩增时的错误结果。近年来，又克隆了三个新的端粒酶基因hTR、TLP 1/TPI和hEST 2/hTRT。应用逆转录-聚合酶链反应（RT-PCR）方法检测了27例膀胱癌组织中hEST 2/hTRT和TLP 1/TPI的表达。27例癌组织中hEST 2/hTRT阳性表达率为100%，TLP 1/TPL阳性表达率为92%。5例正常膀胱组织中hEST 2/hTRT均为阴性表达，TLP 1/TP 1阳性表达率为60%（3/5）。结果表明，RT-PCR检测hEST 2/hTRP基因的表达，可作为膀胱癌筛查或诊断的有效方法。