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人端粒酶的RNA组分(hTR)和催化亚基(hTERT)在非肿瘤性前列腺组织、前列腺上皮内瘤变及前列腺癌中的表达模式

Expression-patterns of the RNA component (hTR)and the catalytic subunit (hTERT) of human telomerase in nonneoplastic prostate tissue, prostatic intraepithelial neoplasia, and prostate cancer.

作者信息

Bettendorf Olaf, Heine Bernhard, Kneif Sören, Eltze Elke, Semjonow Axel, Herbst Hermann, Stein Harald, Böcker Werner, Poremba Christopher

机构信息

Gerhard-Domagk-Institute of Pathology, University of Münster, Münster, Germany.

出版信息

Prostate. 2003 May 1;55(2):99-104. doi: 10.1002/pros.10201.

Abstract

BACKGROUND

Telomerase, a ribonucleoprotein, is composed of a RNA component (hTR) and two protein subunits. One of these subunits, the catalytic subunit (human telomerase reverse transcriptase, hTERT), represents a reverse transcriptase. hTERT-expression is closely correlated with telomerase activity. The telomerase is thought to be involved in immortalization process. By adding hexamic repeats to the end of chromosomal DNA, the telomeres, the enzyme is able to stop progresssive telomeric DNA loss that occurs during cell division due to the end replication problem that stops the mitotic clock.

METHODS

Expression-patterns of hTR using radioactive in situ hybridization with (35)S-labelled RNA probes were compared with immunhistochemical staining for hTERT in 14 cases of archival paraffin-embedded samples of normal prostatic tissue, high-grade prostatic intraepithelial neoplasia (PIN), prostatic cancer, and one atypical adenomatous hyperplasia (AAH). Beside the expression-patterns each telomerase component was evaluated semiquantitatively.

RESULTS

hTERT and hTR can be found in nonneoplstic tissue and are upregulated in premalignant transformated lesions. AAH showed no hTERT-expression and low hTR-expression. There is a heterogenous expression within prostatic carcinomas.

CONCLUSIONS

No association was observed between the grade of the tumour differentiation and semiquantitative levels of hTR- or hTERT-expression. Telomerase is of limited value for the diagnostic of malignant or benign lesions in prostate.

摘要

背景

端粒酶是一种核糖核蛋白,由一个RNA成分(hTR)和两个蛋白质亚基组成。其中一个亚基,即催化亚基(人类端粒酶逆转录酶,hTERT),是一种逆转录酶。hTERT的表达与端粒酶活性密切相关。端粒酶被认为参与了永生化过程。通过在染色体DNA末端添加六核苷酸重复序列(端粒),该酶能够阻止由于末端复制问题导致的细胞分裂过程中端粒DNA的渐进性丢失,而末端复制问题会使有丝分裂时钟停止。

方法

使用放射性原位杂交技术,用(35)S标记的RNA探针检测14例存档石蜡包埋的正常前列腺组织、高级别前列腺上皮内瘤变(PIN)、前列腺癌和1例非典型腺瘤样增生(AAH)样本中hTR的表达模式,并与hTERT的免疫组织化学染色进行比较。除了表达模式外,还对每个端粒酶成分进行了半定量评估。

结果

hTERT和hTR可在非肿瘤组织中发现,并在癌前转化病变中上调。AAH未显示hTERT表达,hTR表达较低。前列腺癌中存在异质性表达。

结论

未观察到肿瘤分化程度与hTR或hTERT表达的半定量水平之间存在关联。端粒酶在前列腺恶性或良性病变的诊断中价值有限。

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