Yu J, Roy D, Brockmeyer A D, Dubeau L
Department of Pathology, USC/Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA 90089-9181, USA.
Br J Cancer. 2007 Jun 18;96(12):1908-13. doi: 10.1038/sj.bjc.6603817. Epub 2007 May 22.
Cell cultures of ovarian cystadenomas transfected with SV40 large T antigen are not immortal because they invariably reach a phenomenon called crisis, which is triggered in part by telomere attrition. Recovery from crisis may be an integral component of the malignant transformation process. We reported earlier that such ovarian cystadenoma cell cultures undergo severe changes in DNA ploidy as they approach crisis and that such changes are an important determinant of crisis independent of telomere attrition. Here, we show that in sharp contrast to these benign ovarian tumours, the DNA content of ovarian tumours of low malignant potential (LMP) was remarkably stable as they approached crisis, suggesting that telomere attrition was the main determinant of this mortality checkpoint. Lack of a ploidy-based crisis was not due to loss of expression of a functional SV40 large T antigen protein. We conclude that ovarian LMP tumours are characterised by increased numerical chromosomal stability compared to cystadenomas. This might account for the fact that most LMP tumours are diploid or near diploid in vivo. This fundamental difference in chromosomal stability between ovarian cystadenomas and LMP tumours also suggests potential differences in predisposition to progression to malignancy between these two ovarian tumour subtypes.
用SV40大T抗原转染的卵巢囊腺瘤细胞培养物不会永生，因为它们总会出现一种叫做危机的现象，这种现象部分由端粒损耗引发。从危机中恢复可能是恶性转化过程的一个组成部分。我们之前报道过，此类卵巢囊腺瘤细胞培养物在接近危机时DNA倍体会发生严重变化，且这些变化是与端粒损耗无关的危机的重要决定因素。在此，我们表明，与这些良性卵巢肿瘤形成鲜明对比的是，低恶性潜能（LMP）卵巢肿瘤在接近危机时DNA含量非常稳定，这表明端粒损耗是这个死亡检查点的主要决定因素。缺乏基于倍体的危机并非由于功能性SV40大T抗原蛋白表达缺失所致。我们得出结论，与囊腺瘤相比，卵巢LMP肿瘤的特征是染色体数目稳定性增加。这可能解释了大多数LMP肿瘤在体内为二倍体或接近二倍体这一事实。卵巢囊腺瘤和LMP肿瘤在染色体稳定性上的这一根本差异也表明这两种卵巢肿瘤亚型在发展为恶性肿瘤的易感性方面可能存在差异。
