Varon D, Jiang C, Hedican C, Dome J S, Umbricht C B, Carey L A, Thompson H J, Sukumar S
Breast Cancer Program, Johns Hopkins Oncology Center, Baltimore, Maryland 21205-2196, USA.
Cancer Res. 1997 Dec 15;57(24):5605-9.
The 1-methyl-1-nitrosourea-induced rat mammary tumor model system is well studied, reproducible, and widely used. We have investigated whether these tumors possess higher telomerase activity than normal mammary tissue. Using the telomeric repeat amplification protocol assay, we found significantly higher telomerase activity in 36 mammary carcinomas than in 72 mammary glands of virgin rats. The level of telomerase activity in virgin rats was unaffected by strain, age, stage of the estrous cycle, or ovariectomy. However, mammary glands obtained from pregnant rats exhibited telomerase activity comparable to that found in the tumors, possibly reflecting the high epithelial content of these tissues. Indeed, isolated epithelial cells from virgin and pregnant mammary glands and from carcinomas had similar telomerase activities. Thus, telomerase activity is constitutive in the rat mammary epithelium and is not a unique characteristic of malignant transformation in this tissue. These results underscore the importance of attributing biochemical properties to specific cell types in a tissue, a situation not paralleled in the interpretation of data from in vitro models.
1-甲基-1-亚硝基脲诱导的大鼠乳腺肿瘤模型系统已得到充分研究，具有可重复性且应用广泛。我们研究了这些肿瘤的端粒酶活性是否高于正常乳腺组织。通过端粒重复序列扩增法检测，我们发现36例乳腺癌中端粒酶活性显著高于72例未孕大鼠的乳腺组织。未孕大鼠的端粒酶活性水平不受品系、年龄、发情周期阶段或卵巢切除术的影响。然而，从妊娠大鼠获取的乳腺组织显示出与肿瘤中相当的端粒酶活性，这可能反映了这些组织中上皮细胞含量较高。事实上，从未孕和妊娠大鼠乳腺组织以及癌组织中分离出的上皮细胞具有相似的端粒酶活性。因此，端粒酶活性在大鼠乳腺上皮细胞中是组成性的，并非该组织恶性转化的独特特征。这些结果强调了在组织中确定特定细胞类型生化特性的重要性，这一情况与体外模型数据解释有所不同。
