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端粒和端粒酶在人类癌症中的作用。

The role of telomeres and telomerase in human cancer.

作者信息

Balasubramanian S, Singh N

机构信息

Department of Biochemistry, All India Institute of Medical Sciences, New Delhi.

出版信息

Indian J Physiol Pharmacol. 1996 Jul;40(3):199-204.

PMID:8950133
Abstract

Human cancers/malignant transformation of normal cells occur from multiple independent genetic changes/mutations that can subvert the normal growth controls of cells, leading to distinct phenotypic changes and immortalization. Normal human somatic cells have limited proliferative capacity both in vitro and in vivo and undergo senescence. Recent studies have implicated telomeres and telomerase in the regulation of lifespan of cells. Telomeres are the stretches of DNA consisting of tandem repeats of nucleotide sequences that cap chromosomes and prevent its degradation and play a role, both in normal control of cell proliferation and abnormal growth of cancers. They are highly conserved during evolution. Telomerase, the novel reverse transcriptase enzyme that synthesizes telomeric DNA is repressed in most human somatic cells, it results in telomere shortening with each cell division, leading to a process thought to contribute to senescence. Recent research proposes that activation of telomerase is important for cells to proliferate indefinitely and that all human cancer cells require activation of this enzyme to maintain telomeric DNA, to overcome cellular senescence and to attain immortality. Thus telomeres and telomerase offer potential for diagnostics, cancer therapy as well as for understanding the process of aging.

摘要

人类癌症/正常细胞的恶性转化源于多个独立的基因变化/突变,这些变化/突变会破坏细胞的正常生长控制,导致明显的表型变化和永生化。正常人类体细胞在体外和体内的增殖能力有限,并会经历衰老。最近的研究表明端粒和端粒酶参与细胞寿命的调节。端粒是由核苷酸序列串联重复组成的DNA片段,它覆盖染色体并防止其降解,在细胞增殖的正常控制和癌症的异常生长中都发挥作用。它们在进化过程中高度保守。端粒酶是一种合成端粒DNA的新型逆转录酶,在大多数人类体细胞中受到抑制,这导致每次细胞分裂后端粒缩短,从而引发一个被认为与衰老有关的过程。最近的研究提出,端粒酶的激活对于细胞无限增殖很重要,并且所有人类癌细胞都需要激活这种酶来维持端粒DNA,克服细胞衰老并实现永生化。因此,端粒和端粒酶在诊断、癌症治疗以及理解衰老过程方面都具有潜力。

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