Telomerase in breast cancer: A critical evaluation

Human chromosomes have highly specialized structures at their ends termed telomeres, repetitive, non-coding DNA sequences (5′-TTAGGG-3′), ranging in size from 5 to 20 kb in human cells. These highly specialized structures prevent chromosome ends from being recognized as double-strand DNA breaks, and they also provide protection from destabilizing agents. The mechanism for maintaining telomere integrity is controlled by telomerase, a ribonucleoprotein enzyme that specifically restores telomere sequences lost during replication by using an intrinsic RNA component as a template for polymerization. Telomerase has two core functional components required for its activity: the catalytic subunit of human telomerase reverse transcriptase (hTERT) and a telomerase RNA template (hTR). Telomerase is activated in the majority of immortal cell lines in culture and in most malignant tumors. This review outlines our current understanding of telomerase in breast cancer development and critically evaluates potential utilities in diagnosis, prognosis, and therapy.