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

Abstract

Background: Cancer cells can employ telomerase or the alternative lengthening of telomeres (ALT) pathway for telomere maintenance. Cancer cells that use the ALT pathway exhibit distinct phenotypes such as heterogeneous telomeres and specialised Promyelocytic leukaemia (PML) nuclear foci called APBs. In our study, we used wild-type PML and a PML mutant, in which the coiled-coil domain is deleted (PML C/C-), to investigate how these proteins can affect telomere maintenance pathways in cancer cells that use either the telomerase or ALT pathway.

Results: 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.

Conclusion: 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.