Forsythe Heidi L, Elmore Lynne W, Jensen Keith O, Landon Melissa R, Holt Shawn E
Department of Pathology, Medical College of Virginia at Virginia Commonwealth University, Richmond 23298-0662, USA.
Int J Oncol. 2002 Jun;20(6):1137-43.
Retroviral infection of hTERT, the catalytic component of telomerase, into BJ fibroblasts (population doubling 28) resulted in reconstitution of telomerase activity, telomere maintenance, and extension of in vitro lifespan. The hTERT-infected cells also exhibited increased growth rate and colony forming efficiency relative to controls, while remaining contact-inhibited and maintaining a p53-mediated damage response following gamma-irradiation. All single cell-derived BJ-hTERT clones grew faster than the hTERT mass cultures and maintained telomeres; however, neither telomerase activity levels nor mean telomere length correlated with the growth rate. Introduction of hTERT rescued aged BJ fibroblasts from senescence via a telomere-dependent mechanism and provided renewed proliferative potential. Collectively, our data indicate that both early and late in the cellular lifespan of human cells, ectopic expression of telomerase using a retroviral system provides a growth advantage while maintaining normal cellular characteristics.
将端粒酶的催化成分hTERT逆转录病毒感染BJ成纤维细胞（群体倍增28次），导致端粒酶活性重建、端粒维持以及体外寿命延长。与对照相比，hTERT感染的细胞还表现出生长速率和集落形成效率增加，同时在γ射线照射后仍保持接触抑制并维持p53介导的损伤反应。所有单细胞来源的BJ-hTERT克隆生长速度均快于hTERT大量培养物并维持端粒；然而，端粒酶活性水平和平均端粒长度均与生长速率无关。hTERT的导入通过端粒依赖性机制使衰老的BJ成纤维细胞免于衰老，并提供了新的增殖潜能。总体而言，我们的数据表明，在人类细胞寿命的早期和晚期，使用逆转录病毒系统异位表达端粒酶在维持正常细胞特征的同时提供了生长优势。
