Meyerson M, Counter C M, Eaton E N, Ellisen L W, Steiner P, Caddle S D, Ziaugra L, Beijersbergen R L, Davidoff M J, Liu Q, Bacchetti S, Haber D A, Weinberg R A
Whitehead Institute for Biomedical Research, Department of Biology, Massachusetts Institute of Technology, Cambridge 02142, USA.
Cell. 1997 Aug 22;90(4):785-95. doi: 10.1016/s0092-8674(00)80538-3.
Telomerase, the ribonucleoprotein enzyme that elongates telomeres, is repressed in normal human somatic cells but is reactivated during tumor progression. We report the cloning of a human gene, hEST2, that shares significant sequence similarity with the telomerase catalytic subunit genes of lower eukaryotes. hEST2 is expressed at high levels in primary tumors, cancer cell lines, and telomerase-positive tissues but is undetectable in telomerase-negative cell lines and differentiated telomerase-negative tissues. Moreover, the message is up-regulated concomitant with the activation of telomerase during the immortalization of cultured cells and down-regulated during in vitro cellular differentiation. Taken together, these observations suggest that the induction of hEST2 mRNA expression is required for the telomerase activation that occurs during cellular immortalization and tumor progression.
端粒酶是一种可延长端粒的核糖核蛋白酶，在正常人体体细胞中受到抑制，但在肿瘤进展过程中会重新激活。我们报告了一个人类基因hEST2的克隆，它与低等真核生物的端粒酶催化亚基基因具有显著的序列相似性。hEST2在原发性肿瘤、癌细胞系和端粒酶阳性组织中高表达，但在端粒酶阴性细胞系和分化的端粒酶阴性组织中检测不到。此外，在培养细胞永生化过程中，该信使RNA随着端粒酶的激活而上调，在体外细胞分化过程中则下调。综上所述，这些观察结果表明，hEST2 mRNA表达的诱导是细胞永生化和肿瘤进展过程中端粒酶激活所必需的。
