Schrader Mark, Burger Angelika M, Müller Markus, Krause Hans, Straub Bernd, Schostak Martin, Schulze Wolfgang, Lauke Heidrun, Miller Kurt
Department of Urology, Universitätsklinikum Benjamin Franklin, Freie Universität Berlin, Hindenburgdamm 30, 12200 Berlin, Germany.
BMC Cancer. 2002 Nov 29;2:32. doi: 10.1186/1471-2407-2-32.
The activity of the ribonucleoprotein enzyme telomerase is detectable in germ, stem and tumor cells. One major component of telomerase is human telomerase reverse transcriptase (hTERT), which encodes the catalytic subunit of telomerase. Here we investigate the correlation of telomerase activity and hTERT gene expression and the differentiation status of primary testicular germ cell tumors (TGCT).
Telomerase activity (TA) was detected by a quantitative telomerase PCR ELISA, and hTERT mRNA expression was quantified by online RT-PCR in 42 primary testicular germ cell tumors. The control group consisted of benign testicular biopsies from infertile patients.
High levels of telomerase activity and hTERT expression were detected in all examined undifferentiated TGCTs and in the benign testicular tissue specimens with germ cell content. In contrast, differentiated teratomas and testicular control tissue without germ cells (Sertoli-cell-only syndrome) showed no telomerase activity and only minimal hTERT expression.
These findings demonstrate an inverse relationship between the level of telomerase activity and hTERT mRNA expression and the differentiation state of germ cell tumors. Quantification of telomerase activity and hTERT mRNA expression enables a new molecular-diagnostic subclassification of germ cell tumors that describes their proliferation potential and differentiation status.
核糖核蛋白酶端粒酶的活性在生殖细胞、干细胞和肿瘤细胞中均可检测到。端粒酶的一个主要成分是人类端粒酶逆转录酶(hTERT),它编码端粒酶的催化亚基。在此,我们研究端粒酶活性与hTERT基因表达以及原发性睾丸生殖细胞肿瘤(TGCT)分化状态之间的相关性。
采用定量端粒酶PCR ELISA检测42例原发性睾丸生殖细胞肿瘤中的端粒酶活性(TA),并通过在线RT-PCR对hTERT mRNA表达进行定量分析。对照组由不育患者的良性睾丸活检组织组成。
在所有检测的未分化TGCT以及含有生殖细胞的良性睾丸组织标本中均检测到高水平的端粒酶活性和hTERT表达。相比之下,分化型畸胎瘤和无生殖细胞的睾丸对照组织(仅支持细胞综合征)未显示端粒酶活性,且hTERT表达极低。
这些发现表明端粒酶活性水平和hTERT mRNA表达与生殖细胞肿瘤的分化状态呈负相关。端粒酶活性和hTERT mRNA表达的定量分析能够对生殖细胞肿瘤进行新的分子诊断亚分类,描述其增殖潜能和分化状态。