Hiyama E, Tatsumoto N, Kodama T, Hiyama K, Shay J, Yokoyama T
HIROSHIMA UNIV,SCH MED,DEPT INTERNAL MED 2,MINAMI KU,HIROSHIMA 734,JAPAN. HIROSHIMA UNIV,SCH MED,DEPT SURG 1,MINAMI KU,HIROSHIMA 734,JAPAN. UNIV TEXAS,SW MED CTR,DEPT CELL BIOL & NEUROSCI,DALLAS,TX 75235.
Int J Oncol. 1996 Sep;9(3):453-8. doi: 10.3892/ijo.9.3.453.
In human somatic cells without the activity of telomerase, the ends of chromosomes consisting of the telomeric repeats TTAGGG progressively erode with each cell division. In germline and immortal cells telomerase activity maintains telomere length and thus compensates for the 'end-replication problem'. Progressive telomere shortening and reactivation of telomerase activity have been considered to be one of the key mechanisms in cellular senescence and immortalization. It has been shown that while most somatic cells do not have detectable telomerase activity, almost all cancers do have telomerase activity. Thus, detection of telomerase activity may have utility in the early diagnosis of cancer and may be a new target for therapeutic intervention. However, there is recent evidence that some cells of renewal tissues, such as hematopoietic cells and basal cells of the epidermis, have detectable telomerase activity. In the present study, we report detectable telomerase activity in normal human intestinal mucosa. This activity is localized to the lower third of each crypt and may be derived from intestinal stem cells. Since intestinal telomeric repeats are shorter in adults when compared to children, the telomerase activity in the intestine is insufficient to maintain telomere length but may be sufficient to provide extended proliferative capacity for such renewal tissues.
在没有端粒酶活性的人体体细胞中，由端粒重复序列TTAGGG组成的染色体末端会随着每次细胞分裂而逐渐缩短。在生殖细胞和永生细胞中，端粒酶活性可维持端粒长度，从而弥补“末端复制问题”。端粒的逐渐缩短和端粒酶活性的重新激活被认为是细胞衰老和永生的关键机制之一。研究表明，虽然大多数体细胞没有可检测到的端粒酶活性，但几乎所有癌症都有端粒酶活性。因此，检测端粒酶活性可能在癌症早期诊断中具有实用价值，并且可能成为治疗干预的新靶点。然而，最近有证据表明，一些更新组织的细胞，如造血细胞和表皮基底细胞，具有可检测到的端粒酶活性。在本研究中，我们报告了在正常人体肠道黏膜中可检测到端粒酶活性。这种活性定位于每个隐窝的下三分之一处，可能来源于肠道干细胞。由于与儿童相比，成年人的肠道端粒重复序列较短，因此肠道中的端粒酶活性不足以维持端粒长度，但可能足以为此类更新组织提供延长的增殖能力。
