Litaker J R, Pan J, Cheung Y, Zhang D K, Liu Y, Wong S C, Wan T S, Tsao S W
Department of Anatomy, Faculty of Medicine, The University of Hong Kong, Hong Kong.
Int J Oncol. 1998 Nov;13(5):951-6. doi: 10.3892/ijo.13.5.951.
Senescence is a specific physiological stage of cells characterized by long population doubling time. It accounts for the inability of normal somatic cells to undergo indefinite cell division. As the number of population doublings increase, cell cycle regulatory mechanisms come into play and signal cells to exit the cell cycle and become senescent. Senescence has been implicated in the aging process and may function as a tumor suppressor mechanism in human cells. The ability to measure the degree of cellular senescence is important in understanding the biological processes regulating cell aging and immortalization. Senescent cells exhibit an enzyme termed senescence-associated histochemical staining. Cells immortalized by viral oncogenes often enter a stage of crisis at the early phase of immortalization. The cells at crisis have a long population doubling time. Cells at the crisis stage resemble senescent cells and the expression of SA- beta-Gal may be used to monitor the process of immortalization. In this study the expression profile of SA-beta-Gal was examined in human ovarian surface epithelial cells (HOSE 6-3) undergoing immortalization by the human papilloma viral oncogene E6 and E7 (HPV E6 and E7). Our results showed a low percentage (12.0%) of HOSE 6-3 cells expressing SA-beta-Gal activity at the pre-crisis stage. The percentage of HOSE 6-3 cells expressing SA-beta-Gal activity was highest (39.2%) at the crisis stage. When HOSE 6-3 cells achieved immortalized status there was a sharp decrease in cells (1. 3%) expressing SA-beta-Gal activity. In addition, an inverse relationship between the expression of SA-beta-Gal activity and telomerase activity was noted in cells undergoing immortalization. The results confirm that the SA-beta-Gal enzyme is a good marker for monitoring the population of cells undergoing senescence at different stages of immortalization and that telomerase activation is a characteristic feature of post-crisis cells.
衰老细胞是细胞的一个特定生理阶段，其特征是群体倍增时间长。这解释了正常体细胞无法进行无限细胞分裂的原因。随着群体倍增次数的增加，细胞周期调控机制开始发挥作用，向细胞发出退出细胞周期并进入衰老状态的信号。衰老与衰老过程有关，可能在人类细胞中作为一种肿瘤抑制机制发挥作用。测量细胞衰老程度的能力对于理解调节细胞衰老和永生化的生物学过程很重要。衰老细胞表现出一种称为衰老相关组织化学染色的酶。由病毒癌基因永生化的细胞在永生化早期通常会进入危机阶段。处于危机阶段的细胞群体倍增时间长。处于危机阶段的细胞类似于衰老细胞，衰老相关β-半乳糖苷酶（SA-β-Gal）的表达可用于监测永生化过程。在本研究中，检测了人乳头瘤病毒癌基因E6和E7（HPV E6和E7）永生化过程中，人卵巢表面上皮细胞（HOSE 6-3）中SA-β-Gal的表达谱。我们的结果显示，在危机前阶段，表达SA-β-Gal活性的HOSE 6-3细胞比例较低（12.0%）。在危机阶段，表达SA-β-Gal活性的HOSE 6-3细胞比例最高（39.2%）。当HOSE 6-3细胞达到永生化状态时，表达SA-β-Gal活性的细胞急剧减少（1.3%）。此外，在永生化细胞中，观察到SA-β-Gal活性表达与端粒酶活性之间呈负相关。结果证实，SA-β-Gal酶是监测永生化不同阶段衰老细胞群体的良好标志物，端粒酶激活是危机后细胞的一个特征。
