Bednarek A K, Chu Y, Aldaz C M
The University of Texas M.D. Anderson Cancer Center, Department of Carcinogenesis, Smithville 78957, USA.
Oncogene. 1998 Jan 22;16(3):381-5. doi: 10.1038/sj.onc.1201553.
To investigate the role of telomerase in estrogen-regulated rodent tissues, we assayed the activity levels of this enzyme and measured cell proliferation and indicators of cellularity in vagina, mammary gland, and uterus from virgin, pregnant, ovariectomized, and ovariectomized estradiol-treated rats. No association was observed between telomerase activity and increased cell proliferation. Telomerase activity was significantly higher (P=0.003) in vagina obtained from ovariectomized rats (very low proliferation) than in vagina from ovariectomized and estradiol-treated rats (high proliferation, high differentiation). The high telomerase levels observed in vagina from ovariectomized rats indicates that the same epithelial compartment (i.e., basal layer) that has the potential to reconstitute the epithelium also contains the cells that express telomerase. The lower telomerase activity in the keratinized (differentiated) vagina was probably due to dilution of the number of telomerase-producing cells by the terminally differentiated non-telomerase-producing cells. Similar results were observed in uterus from ovariectomized versus ovariectomized and estradiol-treated rats. Telomerase activity was highest in uterus from pregnant rats. Telomerase levels in samples from total mammary gland fat pads varied considerably between groups and appeared to be representative of the amount of epithelium present in the sample. Interestingly, when mammary gland samples from the same animals were obtained from pure epithelial organoid preparations, no differences in telomerase activity could be distinguished between animals or groups. Overall these data suggest that telomerase activity, particularly in rat vagina and uterus, appears to be associated with a cell subpopulation showing proliferative and tissue reconstitution potential and not directly associated with proliferation status per se.
为了研究端粒酶在雌激素调节的啮齿动物组织中的作用,我们检测了该酶的活性水平,并测量了来自未交配、怀孕、卵巢切除以及卵巢切除后接受雌二醇治疗的大鼠的阴道、乳腺和子宫中的细胞增殖情况及细胞数量指标。未观察到端粒酶活性与细胞增殖增加之间存在关联。卵巢切除大鼠(增殖水平极低)的阴道中端粒酶活性显著高于卵巢切除并接受雌二醇治疗的大鼠(增殖水平高、分化程度高)的阴道(P = 0.003)。卵巢切除大鼠阴道中观察到的高端粒酶水平表明,具有上皮重建潜力的同一上皮区室(即基底层)也含有表达端粒酶的细胞。角化(分化)阴道中端粒酶活性较低可能是由于终末分化的不产生端粒酶的细胞稀释了产生端粒酶的细胞数量。在卵巢切除大鼠与卵巢切除并接受雌二醇治疗的大鼠的子宫中观察到了类似结果。怀孕大鼠子宫中的端粒酶活性最高。来自整个乳腺脂肪垫的样本中端粒酶水平在各组之间差异很大,似乎代表了样本中上皮组织的数量。有趣的是,当从同一动物的纯上皮类器官制剂中获取乳腺样本时,在动物或组之间无法区分端粒酶活性的差异。总体而言,这些数据表明,端粒酶活性,特别是在大鼠阴道和子宫中,似乎与具有增殖和组织重建潜力的细胞亚群相关,而不是与增殖状态本身直接相关。