Two human breast cancer cell lines showing decreasing telomeric repeat length during early in vitro passaging

Specific DNA repeats serve as a molecular protection shield at the telomeric ends of mammalian chromosomes. The absence of telomerase activity leads to a gradual decrease of telomeric repeat length in normal somatic cells. In contrast, immortalized cells from malignant tumors are usually thought to re-express telomerase to overcome a self-limited growth. Following this hypothesis, re-expression of telomerase is due to a rare mutational event. Herein we describe our results of telomeric length determination in two newly established breast cancer cell lines. During in vitro establishment from pleural effusions, both cell lines showed a marked decrease of the upper border range of telomeric repeat length distribution. The lower border remained within a constant range characteristic for each cell line. In no case was decrease of repeat length accompanied by an increased incidence of telomeric associations or fusions. The results show that a constant telomeric repeat length does not constitute a characteristic feature of immortalized cells. Furthermore, the kinetics of repeat length decrease and the constant range of the lower border reveal that the onset of telomerase activity is not necessarily due to a rare, i.e., mutational, event.