TELOMERASE IN CELLULAR IMMORTALIZATION

端粒，真核细胞染色体的最末端，是 随机重复的专门化序列，涉及 保持染色体稳定性并提供保护 非法重组和酶降解。缩写 被认为是一个“有丝分裂钟”。 最终，当临界阈值水平为 已到达。培养中的人类细胞逃脱衰老并获得 无限期增殖的能力，可能是通过重新激活或 上调端粒酶，从而稳定染色体末端。 与大多数正常人类体细胞相比，端粒酶活性 在永生化细胞系和大约85%的人类中检测到 癌症。端粒酶活性的上调被认为是 赋予癌细胞增殖积累的能力 必要的突变才能变得恶性。那么就可以想象， 抑制端粒酶活性可能会阻止端粒酶永生化 体外培养的细胞及其恶性潜能的获得和/或逆转 体内的恶性表型，从而提供了“证据 端粒酶和细胞之间的因果联系的原理 永生和癌症。端粒酶活性对细胞 永生和致癌，以及端粒酶抑制物， 尤其是针对其RNA部分，可能是有用的化学预防 探员们。这项研究的目标是a)评估端粒酶 拮抗剂在确认端粒酶、细胞 永生和癌症，以及b)评估其作为 化学预防的分子靶标。

Telomeres, the extreme ends of the eukaryotic chromosomes, are tandemly repeated specialized sequences that are implicated in maintaining chromosome stability and providing protection against illegitimate recombination and enzymatic degradation. The shortening of the telomeres is believed to function as a "mitotic clock" eventually signaling senescence when a critical threshold level is reached. Human cells in culture escape senescence and acquire the capability of proliferating indefinitely probably by reactivating or upregulating telomerase and thus stabilizing the chromosomal ends. In contrast to most normal human somatic cells, telomerase activity is detected in immortalized cell lines and in about 85% of human cancers. The upregulation of the telomerase activity is thought to confer upon cancer cells the proliferative capacity to accumulate necessary mutations to become malignant. It is then conceivable that inhibition of the telomerase activity may block immortalization of cells in vitro and acquisition of malignant potential and/or reversal of the malignant phenotype in vivo thus providing "proof of principle" for a causal link between telomerase and cellular immortality and cancer. Telomerase activity is crucial for cellular immortality and carcinogenesis and that telomerase inhibitors, especially against its RNA moiety, may be useful chemopreventive agents. The goal of the study is a) to evaluate telomerase antagonists in validating a causal link between telomerase, cell immortalization, and cancer and b) to assess its appropriateness as a molecular target for chemoprevention.