TITLE:
Telomere Elongation in the Breast Cancer Cell Line 21NT after Treatment with an Epigenetic Modifying Drug
AUTHORS:
Azadeh Motevalli, Hemad Yasaei, Sara Anjomani Virmouni, Morteza Mirabdulhagh, Predrag Slijepcevic, Terry Roberts
KEYWORDS:
Telomere, 5-Aza-2-deoxycytidine (5-aza-CdR), Trichostatin A (TSA), Shelterin, iQ-FISH, Breast Cancer
JOURNAL NAME:
Journal of Cancer Therapy,
Vol.7 No.10,
September
28,
2016
ABSTRACT: Background: Telomere length dysregulation plays a
major role in cancer development and aging. Telomeres are maintained by a group
of specialized genes known as shelterin and shelterin-associated proteins. In
breast cancer lines it has been shown that shelterin proteins are dysregulated thereby affecting the telomere stability and contributing to the neoplastic
conversion of the mammary epithelial cells. Interestingly, the regulation of
some of the shelterin genes is thought
to be controlled epigenetically. Methods and Results: In this study, we set out
to measure the effect of increased shelterin gene expression on telomere length
in breast cancer cell line 21NT treated with 5-aza-2-deoxycytidine (5-aza-CdR)
using known telomere length assays. We measured telomere lengths using:
Telomere Restriction Fragment length (TRF), absolute quantitative-PCR and
cytogenetic Interphase Quantitative Fluorescent in situ Hybridization (iQ-FISH). We found that non-cytotoxic
levels of 5-aza-CdR affect
telomere lengths by causing a significant and stable increase in telomere
lengths of the breast cancer cell line. The increase in telomere lengths was consistently observed when various telomere length methods were used.
Conclusions: Further investigation is required to understand the underlying
mechanism involved, and the significance of telomere length elongation in
relation to clinical outcome when epigenetic modifying drugs are utilized.