Effects of chemopreventive and antitelomerase agents on the spontaneous immortalization of breast epithelial cells
Effects of chemopreventive and antitelomerase agents on the spontaneous immortalization of breast epithelial cells
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DOI：
10.1093/jnci/93.1.39
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发表时间：
2001-01-03
影响因子：
10.3
通讯作者：
Shay, JW
中科院分区：
文献类型：
--
作者：
Herbert, BS;Wright, AC;Shay, JW
背景：端粒酶的激活是乳腺癌和其他癌症发展的早期事件，可能导致细胞永生化，这是癌症进展的关键和限速步骤。来自Li-Fraumeni综合征(LFS)妇女的乳腺上皮细胞在培养中自发地永生化并可复制。因此，我们测试了是否可以通过化学预防药物和抑制端粒酶活性来防止这些细胞永生化。方法：用无毒浓度的化学预防药物奥替拉兹、二氟甲基鸟氨酸、他莫昔芬和维甲酸或两种不同的端粒酶抑制剂处理来自LFS患者的非癌、永生前乳腺上皮细胞3个月。通过一种基于涨落分析的方法估计LFS来源的细胞自发永生化的频率。统计分析是两面性的。结果：长期使用维甲酸可减少LFS来源的乳腺上皮细胞发生自发性永生化事件的频率(P
Background: Activation of telomerase is an early event in the development of breast and other cancers that may lead to cell immortalization, a critical and rate-limiting step in cancer progression. Breast epithelial cells from women with Li-Fraumeni syndrome (LFS) immortalize spontaneously and reproducibly in culture. We, therefore, tested whether immortalization of these cells could be prevented by treating them with chemopreventive agents and by inhibiting telomerase activity, Methods: Noncancerous, preimmortal breast epithelial cells derived from a patient with LFS were treated for 3 months with nontoxic concentrations of the chemopreventive agents oltipraz, difluoromethylornithine, tamoxifen, and retinoic acid or with two different telomerase inhibitors. The frequency of spontaneous immortalization of LFS-derived cells was estimated by an approach based on fluctuation analyses. Statistical analyses were two-sided. Results: The frequency of spontaneous immortalization events of LFS-derived breast epithelial cells was reduced by long-term treatment with retinoic acid (P