Albanell J, Bosl G J, Reuter V E, Engelhardt M, Franco S, Moore M A, Dmitrovsky E
J. Albanell, M. Engelhardt, M. A. S. Moore, Laboratory of Developmental Hematopoiesis, Cell Biology Program, Sloan-Kettering Institute, New York, NY, USA.
J Natl Cancer Inst. 1999 Aug 4;91(15):1321-6. doi: 10.1093/jnci/91.15.1321.
An inverse relationship has been reported between the presence of telomerase enzymatic activity and the induction of differentiation in human tumor cell lines. Male germ cell tumors represent an attractive clinical model to assess this relationship further because high telomerase activity is present in normal germ cell progenitors and in embryonal carcinomas that can differentiate into mature teratomas. To investigate how telomerase activity and the differentiation state of germ cell tumors are related, telomerase activities and telomere lengths were measured in benign testicular tissues, germ cell cancers, and mature or immature teratomas.
By use of a modified telomeric repeat amplification protocol (TRAP) assay, telomerase activity was measured in four specimens of benign testicular tissue, in 27 germ cell cancers, in seven mature teratomas, and in one immature teratoma. Telomere lengths were measured in all specimens by restriction digestion of genomic DNA and Southern blot hybridization analysis. Associations between telomerase activity and tissue histopathology were assessed with two-sided Fisher's exact tests.
Telomerase activity was detected in all examined germ cell cancers and in the benign testicular tissue specimens. In marked contrast, telomerase activity was not detected in any mature teratoma (P<.0001). Very long telomeres were detected in some mature teratomas, consistent with telomerase repression as a late event in teratoma formation. The immature teratoma, with malignant transformation, had high telomerase activity.
Telomerase is active in germ cell cancers and repressed in mature teratomas. The absence of telomerase activity may contribute to the limited proliferative capacity of mature teratomas. These findings support the existence of an inverse relationship between telomerase activity and the differentiation state of clinical germ cell tumors.
据报道，端粒酶活性的存在与人类肿瘤细胞系的分化诱导之间存在负相关关系。男性生殖细胞肿瘤是进一步评估这种关系的有吸引力的临床模型，因为正常生殖细胞祖细胞和可分化为成熟畸胎瘤的胚胎癌中存在高端粒酶活性。为了研究端粒酶活性与生殖细胞肿瘤的分化状态如何相关，我们在良性睾丸组织、生殖细胞癌以及成熟或不成熟畸胎瘤中测量了端粒酶活性和端粒长度。
使用改良的端粒重复序列扩增协议（TRAP）测定法，在4份良性睾丸组织标本、27份生殖细胞癌、7份成熟畸胎瘤和1份不成熟畸胎瘤中测量端粒酶活性。通过对基因组DNA进行限制性消化和Southern印迹杂交分析，在所有标本中测量端粒长度。端粒酶活性与组织组织病理学之间的关联通过双侧Fisher精确检验进行评估。
在所有检测的生殖细胞癌和良性睾丸组织标本中均检测到端粒酶活性。与之形成鲜明对比的是，在任何成熟畸胎瘤中均未检测到端粒酶活性（P<0.0001）。在一些成熟畸胎瘤中检测到非常长的端粒，这与端粒酶抑制是畸胎瘤形成后期事件一致。具有恶性转化的不成熟畸胎瘤具有高端粒酶活性。
端粒酶在生殖细胞癌中活跃，在成熟畸胎瘤中受到抑制。端粒酶活性的缺失可能导致成熟畸胎瘤增殖能力有限。这些发现支持了端粒酶活性与临床生殖细胞肿瘤分化状态之间存在负相关关系。
