短的功能障碍端粒损害了INK4a(delta2/3) 易患癌症的小鼠中的瘤发生
R A Greenberg1, L Chin, A Femino
1Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, New York 10461, USA.
Cell
|May 25, 1999
概括
端粒缩短会损害缺乏端粒酶RNA (mTR) 和INK4a的小鼠的瘤形成. 恢复mTR恢复了促进癌症的潜力,突出显示了端粒维护.
科学领域:
- 癌症生物学 癌症生物学
- 遗传学 是一个遗传学.
- 细胞衰老 细胞衰老
背景情况:
- 保持端粒长度对于癌细胞的存活和增殖至关重要.
- 端粒功能障碍可以作为瘤发生的障碍.
- 端粒生物学与瘤抑制基因之间的相互作用是复杂的.
研究的目的:
- 为了研究端粒功能障碍对小鼠模型瘤形成的影响.
- 评估端粒酶RNA (mTR) 和INK4a在瘤发育中的作用.
- 为了确定端粒酶激活是否对于具有临界短端粒的细胞中恶性转变是必要的.
主要方法:
- 产生了连续几代缺乏端粒酶RNA (mTR) 和INK4a瘤抑制基因的小鼠.
- 在体内评估瘤形成和体内评估瘤潜在的几代人.
- 在缺陷细胞中重新引入mTR以评估瘤潜在的恢复.
主要成果:
- 端粒酶缺乏小鼠的后代显著减少了瘤形成和瘤潜在.
- 在这些后代中观察到严重的端粒缩短和功能障碍.
- 重新引入mTR恢复了具有临界短端粒的细胞中的致癌潜力.
结论:
- 端粒功能的丧失会损害,但不能完全阻止瘤的形成,即使在具有完整的DNA损伤反应的易患癌症的模型中也是如此.
- 端粒酶激活与临界短的端粒合作,促进恶性转变.
- 端粒维护是癌症发展和进展的关键因素.
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