Activation of self-renewal and meiotic genes in tumour cell lines resistant to genotoxic treatment
Date
2014
Authors
Salmiņa, Kristīne
Journal Title
Journal ISSN
Volume Title
Publisher
Latvijas Universitāte
Abstract
Pašatjaunošanās un meijotisko gēnu aktivācija pēc genotoksiskas apstrādes rezistentās audzēju šūnu līnijās
Šajā darbā tika pētīta iespējamā saistība starp poliploīdijas un dzimumšūnu līnijai raksturīgo gēnu indukciju pēc pretvēža apstrādes atkarībā no TP53 statusa un audzēju šūnu rezistence pret DNS bojājumu. Pirmo reizi tika atrasta un citoloģiski raksturota galveno cilmestības transkripcijas faktoru OCT4, NANOG un SOX2 ekspresijas aktivācija, kas izraisīta pārkāpjot tetraploīdo barjeru pēc DNS bojājuma TP53 mutantās, bet ne funkcionālās audzēja šūnas, kā arī galvenā mejotiskā kohezīna REC8 ekspresija somatisko audzēja šūnu līnijās, kas apstrādātas ar jonizējošo starojumu vai topoizomerazes II inhibitoru etopozīdu. Turklāt šajā procesā atrasta arī autofāgijas loma. Kopumā, šie novērojumi raksturo TP53-mutantu audzēja šūnu izdzīvošanas stratēģiju pēc genotoksiskas apstrādes, izmantojot kodola reprogrammēšanu uz embronalitātei līdzīgu stāvokli.
Atslēgvārdi: atgriezeniska poliploīdija, embrionālo cilmes šūnu gēni, limfomu šūnu līnijas, DNS bojājums.
Activation of self-renewal and meiotic genes in tumour cell lines resistant to genotoxic treatment In the present work, a possible link between induction of polyploidy and the germline genes, after anti-cancer treatments depending on TP53 status and resistance of tumour cells to DNA damage was studied. For the first time, the upregulation of the master stemness transcription factors OCT4, NANOG and SOX2 induced by overcoming the tetraploidy barrier in the TP53 mutant but not wild-type tumour cells, as well as expression of the key meiotic cohesin REC8 in somatic tumour cell lines treated with ionizing irradiation or topoisomerase II inhibitor etoposide were found and cytologically characterised. The role of chromatin autophagy in this process was also described. Collectively, these observations characterise survival strategy of TP53-mutant tumour cells by recovering after genotoxic treatments through nuclear reprogramming to the embryonal-like state. Keywords: reversible polyploidy, embryonal stem cell genes, lymphoma cell lines, DNA damage
Activation of self-renewal and meiotic genes in tumour cell lines resistant to genotoxic treatment In the present work, a possible link between induction of polyploidy and the germline genes, after anti-cancer treatments depending on TP53 status and resistance of tumour cells to DNA damage was studied. For the first time, the upregulation of the master stemness transcription factors OCT4, NANOG and SOX2 induced by overcoming the tetraploidy barrier in the TP53 mutant but not wild-type tumour cells, as well as expression of the key meiotic cohesin REC8 in somatic tumour cell lines treated with ionizing irradiation or topoisomerase II inhibitor etoposide were found and cytologically characterised. The role of chromatin autophagy in this process was also described. Collectively, these observations characterise survival strategy of TP53-mutant tumour cells by recovering after genotoxic treatments through nuclear reprogramming to the embryonal-like state. Keywords: reversible polyploidy, embryonal stem cell genes, lymphoma cell lines, DNA damage
Description
Keywords
Bioloģija , Dzīvās dabas zinātnes , Molecular Biology and Biochemistry , reversible polyploidy , embryonal stem cell genes , lymphoma cell lines , DNA damage , atgriezeniska poliploīdija , embrionālo cilmes šūnu gēni , limfomu šūnu līnijas , DNS bojājums