Author(s)

Azadeh Motevalli^1,2, Hemad Yasaei^1,3, Sara Anjomani Virmouni^1,4, Morteza Mirabdulhagh⁵, Predrag Slijepcevic¹, Terry Roberts^1,6*

¹Department of Life Sciences, College of Health and Life Sciences, Brunel University London, Uxbridge, UK.
²Department of Cancer Immunotherapeutics and Tumour Immunology, City of Hope Comprehensive Cancer Centre, Beckman Centre, Duarte, CA, USA.
³School of Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
⁴The Institute of Cancer Research, Chester Beatty Laboratories, London, UK.
⁵Faculty of Life Sciences and Medicine, School of Medical Education, Kings College London, London, UK.
⁶Health and Environment Theme, Institute of Environment, Health and Societies, Brunel University London, Uxbridge, UK.

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.

Telomere, 5-Aza-2-deoxycytidine (5-aza-CdR), Trichostatin A (TSA), Shelterin, iQ-FISH, Breast Cancer

Motevalli, A. , Yasaei, H. , Virmouni, S. , Mirabdulhagh, M. , Slijepcevic, P. and Roberts, T. (2016) Telomere Elongation in the Breast Cancer Cell Line 21NT after Treatment with an Epigenetic Modifying Drug. Journal of Cancer Therapy, 7, 700-711. doi: 10.4236/jct.2016.710072.