Cukusić A, Ivanković M, Skrobot N, Ferenac M, Gotić I, Matijasić M, Polancec D, Rubelj I
Department of Molecular Biology, Ruder Boskovic Institute, Bijenicka 54, 10 000 Zagreb, Croatia.
Cell Prolif. 2006 Jun;39(3):205-16. doi: 10.1111/j.1365-2184.2006.00383.x.
Normal human somatic cells have a limited division potential when they grow in vitro. It is believed that shortening of telomeres, specialized structures at the ends of chromosomes, controls cell growth. When one telomere achieves a critical minimal length, the cell cycle control mechanism recognizes it as DNA damage and causes the cell's exit from the cycle in G1-phase. Because it is not possible to extend telomeres in normal cells, this non-dividing state is prolonged indefinitely, and is known as cellular senescence. The immortal cell line MDA-MB-231 has active telomerase, which prevents telomere shortening and allows cells' permanent divisions. However, there is a fraction of cells that do not divide over several days in culture as documented for some other tumour cell lines. Combination of methods has made it possible to isolate these non-growing cells and compare them with the fraction of fast-growing cells from the same culture. Although the non-growing fraction contains a significant percentage of typical senescent cells, both fractions have equal telomerase activity and telomere length. In this paper we discuss possible mechanisms that cause the appearance of this non-growing fraction of cells in cultures of MDA-MB-231, which indicate stress and genome instability rather than variation in telomerase activity or telomere shortening to affect individual cells.
正常人体体细胞在体外培养时具有有限的分裂潜能。人们认为，端粒（染色体末端的特殊结构）的缩短控制着细胞的生长。当一个端粒达到临界最小长度时，细胞周期控制机制将其识别为DNA损伤，并导致细胞在G1期退出细胞周期。由于正常细胞中无法延长端粒，这种非分裂状态会无限期延长，这就是细胞衰老。永生化细胞系MDA-MB-231具有活跃的端粒酶，可防止端粒缩短并使细胞能够永久分裂。然而，正如其他一些肿瘤细胞系所记录的那样，在培养过程中有一部分细胞在数天内不分裂。多种方法的结合使得分离这些不生长的细胞并将它们与来自同一培养物的快速生长细胞部分进行比较成为可能。尽管不生长部分含有相当比例的典型衰老细胞，但这两个部分的端粒酶活性和端粒长度相等。在本文中，我们讨论了导致MDA-MB-231培养物中出现这种不生长细胞部分的可能机制，这些机制表明应激和基因组不稳定而非端粒酶活性变化或端粒缩短影响单个细胞。
