Stable expression of promyelocytic leukaemia (PML) protein in telomerase positive MCF7 cells results in alternative lengthening of telomeres phenotype

Stable over-expression of both types of PML does not affect the telomere maintenance in the ALT cells. We report novel observations in PML over-expressed telomerase-positive MCF7 cells: 1) APBs are detected in telomerase-positive MCF7 cells following over-expression of wild-type PML and 2) rapid telomere elongation is observed in MCF7 cells that stably express either wild-type PML or PML C/C-. We also show that the telomerase activity in MCF7 cells can be affected depending on the type of PML protein over-expressed.Our data suggests that APBs might not be essential for the ALT pathway as MCF7 cells that do not contain APBs exhibit long telomeres. We propose that wild-type PML can either definitively dominate over telomerase or enhance the activity of telomerase, and PML C/C- can allow for the co-existence of both telomerase and ALT pathways. Our findings add another dimension in the study of telomere maintenance as the expression of PML alone (wild-type or otherwise) is able to change the dynamics of the telomerase pathway.Telomeres are specialised chromatin structures capping the ends of chromosomes [1]. They consist of TTAGGG repeats and function to protect the ends of the DNA. Human telomeres in somatic cells lose about 50 to 150 base pairs with each round of cellular division. When telomeres shorten to a critical length, cells will enter a state of permanent growth arrest termed as replicative senescence. Cellular senescence limits the proliferative capacity of cells and this suppresses tumourigenesis [2]. To overcome cellular senescence and to achieve immortality, cancer cells maintain telomeres through the activation of the telomerase enzyme. Some cancer cells also use the lesser-known telomere maintenance pathway-the Alternative Lengthening of Telomeres pathway, ALT [3,4].Cancer cells that employ the ALT pathway for telomere maintenance exhibit distinct hallmarks from cells that use telomerase [5]. These cells exhibit heterogeneous telomeres, with length vary