Wan T S, Martens U M, Poon S S, Tsao S W, Chan L C, Lansdorp P M
Department of Anatomy, Faculty of Medicine, University of Hong Kong, Hong Kong.
Genes Chromosomes Cancer. 1999 Jan;24(1):83-6. doi: 10.1002/(sici)1098-2264(199901)24:1<83::aid-gcc12>3.0.co;2-c.
Human ovarian surface epithelial (HOSE) cells transfected with the E6 and E7 oncogenes of the human papilloma virus (PV) do not express measurable telomerase activity. Relative to untransfected control cells, HOSE-PV cells have an extended in vitro lifespan characterized by a very high frequency of telomeric associations (TAs) of chromosomes. In order to study the role of telomere shortening in the formation of TAs, we studied the telomere length in 120 dicentric chromosomes in HOSE-PV cells by using quantitative fluorescence in situ hybridization. Forty percent of the dicentric chromosomes had no fluorescence signal at the junction site, and in the remainder the fluorescence at the junction was less than at corresponding unjoined ends. These observations support a critical role of telomere shortening in the development of TAs and the subsequent genetic instability observed in a majority of tumor cells.
转染人乳头瘤病毒(PV)E6和E7癌基因的人卵巢表面上皮(HOSE)细胞不表达可检测到的端粒酶活性。相对于未转染的对照细胞,HOSE-PV细胞在体外具有延长的寿命,其特征是染色体端粒联合(TA)的频率非常高。为了研究端粒缩短在TA形成中的作用,我们通过定量荧光原位杂交研究了HOSE-PV细胞中120条双着丝粒染色体的端粒长度。40%的双着丝粒染色体在连接处没有荧光信号,其余的连接处荧光强度低于相应未连接的末端。这些观察结果支持端粒缩短在TA形成以及大多数肿瘤细胞中随后观察到的遗传不稳定性发展中起关键作用。