Chadeneau C, Siegel P, Harley C B, Muller W J, Bacchetti S
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
Oncogene. 1995 Sep 7;11(5):893-8.
Telomere shortening may contribute to the limited lifespan of somatic cells and telomerase, the enzyme that elongates telomeric DNA and maintains telomere length, may be essential for unlimited cell proliferation in vivo and in vitro. Telomerase is not expressed in most human somatic cells but is a nearly ubiquitous tumour marker, being activated in malignant cells from many cancers. Inhibition of telomerase may lead to telomere shortening and eventually limit the proliferative capacity of malignant cells and hence be of therapeutic value. With the intent of characterizing an animal model for inhibition studies, we investigated telomerase activity during mammary tumorigenesis in transgenic mice overexpressing the neu gene. We detected activity in primary mammary tumours and lung metastases but also in normal mammary glands and other organs. Activity was elevated in tumors versus normal tissues and was enhanced by short-term culturing of normal cells. Telomerase activity was also present in somatic tissues from the non-transgenic parental strain and the outbred Mus spretus strain. As we recently detected telomerase activity in normal human hemopoietic tissues, mouse models of tumorigenesis may provide useful experimental systems for assessing the outcome of in vivo inhibition of telomerase in both malignant and normal cells.
端粒缩短可能导致体细胞寿命有限，而端粒酶，即一种可延长端粒DNA并维持端粒长度的酶，对于体内外细胞的无限增殖可能至关重要。端粒酶在大多数人类体细胞中不表达，但几乎是一种普遍存在的肿瘤标志物，在许多癌症的恶性细胞中被激活。抑制端粒酶可能导致端粒缩短，并最终限制恶性细胞的增殖能力，因此具有治疗价值。为了建立用于抑制研究的动物模型，我们研究了过表达neu基因的转基因小鼠乳腺肿瘤发生过程中端粒酶的活性。我们在原发性乳腺肿瘤和肺转移灶中检测到了活性，在正常乳腺和其他器官中也检测到了活性。肿瘤中的活性高于正常组织，并且通过正常细胞的短期培养而增强。端粒酶活性也存在于非转基因亲本品系和远交系小家鼠的体细胞组织中。由于我们最近在正常人造血组织中检测到了端粒酶活性，肿瘤发生的小鼠模型可能为评估体内抑制端粒酶对恶性细胞和正常细胞的影响提供有用的实验系统。
