Upregulation of meiosis-specific genes in lymphoma cell lines following genotoxic insult and induction of mitotic catastrophe.
Authors
Kalejs, MartinsIvanov, Andrei
Plakhins, Gregory
Cragg, Mark S
Emzinsh, Dzintars
Illidge, Timothy M
Erenpreisa, Jekaterina
Affiliation
Biomedical Research and Study Centre, Latvian University, Ratsupites 1, Riga, LV-1067, Latvia. m.kalejs@no.lvIssue Date
2006
Metadata
Show full item recordAbstract
BACKGROUND: We have previously reported that p53 mutated radioresistant lymphoma cell lines undergo mitotic catastrophe after irradiation, resulting in metaphase arrest and the generation of endopolyploid cells. A proportion of these endopolyploid cells then undergo a process of de-polyploidisation, stages of which are partially reminiscent of meiotic prophase. Furthermore, expression of meiosis-specific proteins of the cancer/testis antigens group of genes has previously been reported in tumours. We therefore investigated whether expression of meiosis-specific genes was associated with the polyploidy response in our tumour model. METHODS: Three lymphoma cell lines, Namalwa, WI-L2-NS and TK6, of varying p53 status were exposed to a single 10 Gy dose of gamma radiation and their responses assessed over an extended time course. DNA flow cytometry and mitotic counts were used to assess the kinetics and extent of polyploidisation and mitotic progression. Expression of meiotic genes was analysed using RT-PCR and western blotting. In addition, localisation of the meiotic cohesin REC8 and its relation to centromeres was analysed by immunofluorescence. RESULTS: The principal meiotic regulator MOS was found to be significantly post-transcriptionally up-regulated after irradiation in p53 mutated but not p53 wild-type lymphoma cells. The maximum expression of MOS coincided with the maximal fraction of metaphase arrested cells and was directly proportional to both the extent of the arrest and the number of endopolyploid cells that subsequently emerged. The meiotic cohesin REC8 was also found to be up-regulated after irradiation, linking sister chromatid centromeres in the metaphase-arrested and subsequent giant cells. Finally, RT-PCR revealed expression of the meiosis-prophase genes, DMC1, STAG3, SYCP3 and SYCP1. CONCLUSION: We conclude that multiple meiotic genes are aberrantly activated during mitotic catastrophe in p53 mutated lymphoma cells after irradiation. Furthermore, we suggest that the coordinated expression of MOS and REC8 regulate the extent of arrested mitoses and polyploidy.Citation
Upregulation of meiosis-specific genes in lymphoma cell lines following genotoxic insult and induction of mitotic catastrophe. 2006, 6:6 BMC CancerJournal
BMC CancerDOI
10.1186/1471-2407-6-6PubMed ID
16401344Type
ArticleLanguage
enISSN
1471-2407ae974a485f413a2113503eed53cd6c53
10.1186/1471-2407-6-6
Scopus Count
Collections
Related articles
- The role of meiotic cohesin REC8 in chromosome segregation in gamma irradiation-induced endopolyploid tumour cells.
- Authors: Erenpreisa J, Cragg MS, Salmina K, Hausmann M, Scherthan H
- Issue date: 2009 Sep 10
- Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells.
- Authors: Salmina K, Jankevics E, Huna A, Perminov D, Radovica I, Klymenko T, Ivanov A, Jascenko E, Scherthan H, Cragg M, Erenpreisa J
- Issue date: 2010 Aug 1
- Mitotic catastrophe and endomitosis in tumour cells: an evolutionary key to a molecular solution.
- Authors: Erenpreisa J, Kalejs M, Cragg MS
- Issue date: 2005 Dec
- Activation of meiosis-specific genes is associated with depolyploidization of human tumor cells following radiation-induced mitotic catastrophe.
- Authors: Ianzini F, Kosmacek EA, Nelson ES, Napoli E, Erenpreisa J, Kalejs M, Mackey MA
- Issue date: 2009 Mar 15
- c-Mos forces the mitotic cell cycle to undergo meiosis II to produce haploid gametes.
- Authors: Tachibana K, Tanaka D, Isobe T, Kishimoto T
- Issue date: 2000 Dec 19