Possible new function of telomerase

端粒酶是一种能延长真核细胞染色体两端端粒DNA的酶，为细胞提供无限的增殖寿命。然而，我们的结果表明，在表达端粒酶的人体细胞中，端粒酶比端粒酶参与的更多。一些体细胞在体外继续增殖到端粒缩短的极限，并通过细胞衰老停止增殖，但另一些体细胞在端粒缩短之前就通过培养休克或过早衰老停止了增殖。这些人类体细胞在导入T抗原基因后可以增殖到端粒侵蚀的最终末端，其基因产物可使抑癌基因产物P53和Rb失活。令人意想不到的是，将端粒酶基因(HTERT)导入人体体细胞也能延长细胞的增殖寿命，有时还能使细胞永生(无限增殖寿命)。我们通过蛋白质组分析，在端粒酶导入的人类体细胞中寻找促进细胞继续增殖的细胞蛋白。我们通过MAS分析，从引入hTERT后增加或减少的2D-凝胶斑点中鉴定出许多蛋白质。这些蛋白质在延长寿命方面的作用将被研究。端粒酶的其他可能作用与基因组完整性有关。端粒酶导入的人体细胞表现出对染色体畸变和外源遗传物质整合的抗性。这些特性有利于具有端粒酶活性的体细胞在整个生命周期内继续增殖，维持低致瘤性。

Telomerase is known as an enzyme that elongates telomere DNA at each chromosome end of eukaryotic cells providing cells indefinite proliferative lifespan. However, our results suggested that telomerase participated more than that in telomerase-expressing human somatic cells. Some human somatic cells in vitro continue proliferation to the limit of telomere shortening and ceased proliferation by cellular senescence but other somatic cells cease proliferation by culture shock or premature senescence far before telomere shortening. These human somatic cells can proliferate to the final end of telomere erosion after the introduction of T-antigen gene whose gene product inactivates tumor suppressor gene products as p53 and RB. Unexpectedly, introduction of telomerase gene (hTERT) into human somatic cells also extended proliferative lifespan and sometimes made cells immortal (infinite proliferative lifespan). We searched for cellular proteins, by proteome analysis, that facilitated cells for continued proliferation in telomerase introduced human somatic cells. We identified many proteins, by MAS analysis, from 2D-gel spots that were increased or decreased after introduction of hTERT. Role of these proteins on lifespan extension will be examined. Other possible role of telomerase is on genome integrity. Telomerase-introduced human somatic cells showed resistance against chromosome aberration and integration of exogenous genetic materials. These characteristics are favorable for the function of somatic stem cells, which harbor telomerase activity, to continue proliferation during whole human lifespan and to maintain low tumorigenicity.