TELOMERASE ACTIVITY IN HUMAN OVARIAN-CARCINOMA
TELOMERASE ACTIVITY IN HUMAN OVARIAN-CARCINOMA
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DOI：
10.1073/pnas.91.8.2900
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发表时间：
1994-04-12
影响因子：
11.1
通讯作者：
HARLEY, CB
中科院分区：
文献类型：
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作者：
COUNTER, CM;HIRTE, HW;HARLEY, CB
端粒具有保护真核生物染色体免于非法重组和降解的双重功能，并可能有助于染色体附着到核膜上。我们先前已经表明，端粒酶，合成端粒DNA的酶，在正常的体细胞中检测不到，端粒缩短复制年龄。在体外永生化的细胞中，端粒酶的激活显然稳定了端粒长度，防止了染色体的关键不稳定，即使端粒很短，细胞增殖也会继续。在体内，大多数肿瘤的端粒比对照组织的端粒短，这表明酶具有类似的作用。为了评估端粒酶和端粒稳定性在肿瘤发展和进展中的相关性，我们测量了上皮性卵巢癌转移细胞中的酶活性和端粒长度。我们报告说，极短的端粒维持在这些细胞和肿瘤细胞，但不是同基因的非恶性细胞，表达端粒酶。我们的研究结果表明，恶性肿瘤的进展最终取决于端粒酶的激活，端粒酶抑制剂可能是有效的抗肿瘤药物。
Telomeres fulfill the dual function of protecting eukaryotic chromosomes from illegitimate recombination and degradation and may aid in chromosome attachment to the nuclear membrane. We have previously shown that telomerase, the enzyme which synthesizes telomeric DNA, is not detected in normal somatic cells and that telomeres shorten with replicative age. In cells immortalized in vitro, activation of telomerase apparently stabilizes telomere length, preventing a critical destabilization of chromosomes, and cell proliferation continues even when telomeres are short. In vivo, telomeres of most tumors are shorter than telomeres of control tissues, suggesting an analogous role for the enzyme. To assess the relevance of telomerase and telomere stability in the development and progression of tumors, we have measured enzyme activity and telomere length in metastatic cells of epithelial ovarian carcinoma. We report that extremely short telomeres are maintained in these cells and that tumor cells, but not isogenic nonmalignant cells, express telomerase. Our findings suggest that progression of malignancy is ultimately dependent upon activation of telomerase and that telomerase inhibitors may be effective antitumor drugs.