title: The effect of chemotherapeutic agents on telomere length maintenance in breast cancer cell lines.
abstract: Mammalian telomeric DNA consists of tandem repeats of the sequence TTAGGG associated with a specialized set of proteins, known collectively as Shelterin. These telosomal proteins protect the ends of chromosomes against end-to-end fusion and degradation. Short telomeres in breast cancer cells confer telomere dysfunction and this can be related to Shelterin proteins and their level of expression in breast cancer cell lines. This study investigates whether expression of Shelterin and Shelterin-associated proteins are altered, and influence the protection and maintenance of telomeres, in breast cancer cells. 5-aza-2'-deoxycytidine (5-aza-CdR) and trichostatin A (TSA) were used in an attempt to reactivate the expression of silenced genes. Our studies have shown that Shelterin and Shelterin-associated genes were down-regulated in breast cancer cell lines; this may be due to epigenetic modification of DNA as the promoter region of POT1 was found to be partially methylated. Shelterin genes expression was up-regulated upon treatment of 21NT breast cancer cells with 5-aza-CdR and TSA. The telomere length of treated 21NT cells was measured by q-PCR showed an increase in telomere length at different time points. Our studies have shown that down-regulation of Shelterin genes is partially due to methylation in some epithelial breast cancer cell lines. Removal of epigenetic silencing results in up-regulation of Shelterin and Shelterin-associated genes which can then lead to telomere length elongation and stability.
authors.affiliation: Biosciences, School of Health Sciences & Social Care, Brunel University, Uxbridge, UB8 3PH, UK.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Motevalli
authors.forename: Hemad
authors.initials: H
authors.lastname: Yasaei
authors.forename: Sara Anjomani
authors.initials: SA
authors.lastname: Virmouni
authors.forename: Predrag
authors.initials: P
authors.lastname: Slijepcevic
authors.forename: Terry
authors.initials: T
authors.lastname: Roberts
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D004247:DNA / Q000235:genetics; D019175:DNA Methylation / Q000235:genetics; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology*; D061986:MCF-7 Cells; D008780:Methyltransferases / Q000037:antagonists & inhibitors; D011401:Promoter Regions, Genetic / Q000235:genetics; D000089804:Shelterin Complex; D016615:Telomere / Q000187:drug effects / Q000502:physiology; D059505:Telomere Homeostasis / Q000187:drug effects*; D034501:Telomere-Binding Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D000970:Antineoplastic Agents; D006657:Histones; D006877:Hydroxamic Acids; C440849:POT1 protein, human; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; C012589:trichostatin A; D000077209:Decitabine; D004247:DNA; D008780:Methyltransferases; D001374:Azacitidine