Amplification of telomeric DNA directly correlates with metastatic potential of human and murine cancers of various histological origin.
Telomeres, repeated DNA sequences (T2AG3)n that guard the ends of chromosomes, serve as a checkpoint for cell-cycle progression and regulate cell senescence and apoptosis. Loss of the telomeric repeats promotes genomic instability, which is the hallmark of most cancer cells. Whether this loss differs among tumor cells with malignant potential is unknown and was the goal of this study. An all-human telomeric DNA probe was used to perform fluorescence in situ hybridization (FISH) and the telomeric signals in interphase nuclei were quantitated using a computer software package. Southern blot analysis was carried out to measure terminal restriction fragment length (TRFL) in multiple cancer cell lines, including nonmetastatic and metastatic human breast, lung, prostate, colon, brain, and renal carcinomas, as well as human and murine melanoma clones and somatic cell hybrids. The metastatic capability of all cell lines, clones and somatic cell hybrids was evaluated subsequent to orthotopic implantation into nude mice. FISH preparations with telomeric DNA probes showed that the mean percent telomeric area in the metastatic nuclei was significantly greater than their nonmetastatic counterparts and Southern blotting in selected samples confirmed our findings. These data suggest that amplification of telomeres is directly correlated with invasive and metastatic potential of murine or human tumor cells.
Multani, AS; Ozen, M; Sen, S; Mandal, AK; Price, JE; Fan, D; Radinsky, R; Ali-Osman, F; Von Eschenbach, AC; Fidler, IJ; Pathak, S
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