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端粒DNA:人类前列腺癌发展的标志物?

Telomeric DNA: marker for human prostate cancer development?

作者信息

Ozen M, Imam S A, Datar R H, Multani A S, Narayanan R, Chung L W, von Eschenbach A C, Pathak S

机构信息

Department of Cell Biology, The University of Texas M.D. Anderson Cancer Center, Houston, USA.

出版信息

Prostate. 1998 Sep 1;36(4):264-71. doi: 10.1002/(sici)1097-0045(19980901)36:4<264::aid-pros8>3.0.co;2-f.

DOI:10.1002/(sici)1097-0045(19980901)36:4<264::aid-pros8>3.0.co;2-f
PMID:9719027
Abstract

BACKGROUND

Telomeres that protect chromosomes at both ends are shortened with each somatic cell division through replication-dependent sequence loss at DNA termini. The chromosomes with shortened telomeres tend to become unstable, leading to cell death. Due largely to reactivation/upregulation of telomerase, a ribonucleoprotein that adds nucleotide sequences onto chromosome ends, cancer cells become immortal and neoplastically transformed.

METHODS

The purpose of the present study was to study three newly established human prostate cancer cell lines and three prostate-derived fibroblastic cell cultures at different passages for telomeric DNA signal intensity, telomeric restriction fragment length (TRFL), telomerase activity, and spontaneous apoptotic index.

RESULTS

Compared with the three fibroblastic cell cultures, the three new prostate cancer cell lines showed: 1) telomerase activity, 2) stronger telomeric signals, 3) relatively longer TRFLs, and 4) much lower apoptotic indices. On the other hand, three fibroblastic cell cultures showed: 1) no telomerase activity, 2) weaker telomeric signals, 3) shorter TRFLs (fibroblasts derived from surrounding tissue of prostate tumor showed intermediate TRFLs), and 4) comparatively higher apoptotic indices.

CONCLUSIONS

Based on these results, we conclude that telomeric DNA signal intensity, TRFL, and telomerase activity can be used to distinguish prostate cancer cells from adjacent fibroblasts.

摘要

背景

位于染色体两端起保护作用的端粒,会随着每一次体细胞分裂,因DNA末端依赖复制的序列丢失而缩短。端粒缩短的染色体往往会变得不稳定,从而导致细胞死亡。癌细胞因端粒酶(一种能在染色体末端添加核苷酸序列的核糖核蛋白)的重新激活/上调,而具有永生性并发生肿瘤转化。

方法

本研究旨在对三种新建立的人前列腺癌细胞系和三种不同传代的前列腺来源的成纤维细胞培养物进行端粒DNA信号强度、端粒限制性片段长度(TRFL)、端粒酶活性及自发凋亡指数的研究。

结果

与三种成纤维细胞培养物相比,三种新的前列腺癌细胞系表现出:1)端粒酶活性;2)更强的端粒信号;3)相对更长的TRFL;4)低得多的凋亡指数。另一方面,三种成纤维细胞培养物表现出:1)无端粒酶活性;2)较弱的端粒信号;3)较短的TRFL(来自前列腺肿瘤周围组织的成纤维细胞显示出中等长度的TRFL);4)相对较高的凋亡指数。

结论

基于这些结果,我们得出结论,端粒DNA信号强度、TRFL和端粒酶活性可用于区分前列腺癌细胞与相邻的成纤维细胞。

相似文献

1
Telomeric DNA: marker for human prostate cancer development?端粒DNA:人类前列腺癌发展的标志物?
Prostate. 1998 Sep 1;36(4):264-71. doi: 10.1002/(sici)1097-0045(19980901)36:4<264::aid-pros8>3.0.co;2-f.
2
Telomere length and telomerase activity in bladder and prostate cancer cell lines.膀胱和前列腺癌细胞系中的端粒长度与端粒酶活性
Int J Urol. 1997 Jul;4(4):407-10. doi: 10.1111/j.1442-2042.1997.tb00216.x.
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Telomerase activity in small-cell and non-small-cell lung cancers.小细胞肺癌和非小细胞肺癌中的端粒酶活性。
J Natl Cancer Inst. 1995 Jun 21;87(12):895-902. doi: 10.1093/jnci/87.12.895.
4
A repressor function for telomerase activity in telomerase-negative immortal cells.端粒酶阴性永生化细胞中端粒酶活性的阻遏功能。
Mol Carcinog. 1998 Jan;21(1):17-25. doi: 10.1002/(sici)1098-2744(199801)21:1<17::aid-mc4>3.0.co;2-m.
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Telomere dynamics, end-to-end fusions and telomerase activation during the human fibroblast immortalization process.人成纤维细胞永生化过程中的端粒动力学、端对端融合及端粒酶激活
Oncogene. 1999 Jul 22;18(29):4211-23. doi: 10.1038/sj.onc.1202797.
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Telomerase activity in human renal cell carcinoma.人肾细胞癌中的端粒酶活性
Oncogene. 1996 Jul 4;13(1):161-6.
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Development of retinoblastoma in the absence of telomerase activity.在缺乏端粒酶活性的情况下视网膜母细胞瘤的发生。
J Natl Cancer Inst. 1996 Aug 21;88(16):1152-7. doi: 10.1093/jnci/88.16.1152.
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Spontaneous regression of cutaneous melanoma in sinclair swine is associated with defective telomerase activity and extensive telomere erosion.辛克莱猪皮肤黑色素瘤的自发消退与端粒酶活性缺陷和广泛的端粒侵蚀有关。
Int J Oncol. 2000 Dec;17(6):1219-24. doi: 10.3892/ijo.17.6.1219.
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An alternate splicing variant of the human telomerase catalytic subunit inhibits telomerase activity.人类端粒酶催化亚基的一种可变剪接变体可抑制端粒酶活性。
Neoplasia. 2000 Sep-Oct;2(5):433-40. doi: 10.1038/sj.neo.7900113.

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Caspase-dependent apoptosis induced by telomere cleavage and TRF2 loss.端粒切割和TRF2缺失诱导的半胱天冬酶依赖性凋亡。
Neoplasia. 2000 Jul-Aug;2(4):339-45. doi: 10.1038/sj.neo.7900105.