Upregulation of meiosis-specific genes in lymphoma cell lines following genotoxic insult and induction of mitotic catastrophe
Upregulation of meiosis-specific genes in lymphoma cell lines following genotoxic insult and induction of mitotic catastrophe
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.
Kalejs, Martins
74194c4c-fdb4-4fd7-b25d-f46ab5f0cc4b
Ivanov, Andrey
0b43b5f4-c35e-4ee8-9fd6-cffe3bbefb1e
Plakhins, Gregory
ba250554-8212-43f5-b71b-aa3408c34104
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Emzinsh, Dzintars
92e8a025-3272-45ba-acc2-4f3991b18ab4
Illidge, Timothy M.
003bddd7-d778-4c77-bcaa-3b71b364d9a1
Erenpreisa, Jekaterina
70b5fecb-7208-431f-bd35-ec498edc0033
2006
Kalejs, Martins
74194c4c-fdb4-4fd7-b25d-f46ab5f0cc4b
Ivanov, Andrey
0b43b5f4-c35e-4ee8-9fd6-cffe3bbefb1e
Plakhins, Gregory
ba250554-8212-43f5-b71b-aa3408c34104
Cragg, Mark S.
ec97f80e-f3c8-49b7-a960-20dff648b78c
Emzinsh, Dzintars
92e8a025-3272-45ba-acc2-4f3991b18ab4
Illidge, Timothy M.
003bddd7-d778-4c77-bcaa-3b71b364d9a1
Erenpreisa, Jekaterina
70b5fecb-7208-431f-bd35-ec498edc0033
Kalejs, Martins, Ivanov, Andrey, Plakhins, Gregory, Cragg, Mark S., Emzinsh, Dzintars, Illidge, Timothy M. and Erenpreisa, Jekaterina
(2006)
Upregulation of meiosis-specific genes in lymphoma cell lines following genotoxic insult and induction of mitotic catastrophe.
BMC cancer, 6 (6).
(doi:10.1186/1471-2407-6-6).
Abstract
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.
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Published date: 2006
Additional Information:
Research article
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Local EPrints ID: 26418
URI: http://eprints.soton.ac.uk/id/eprint/26418
ISSN: 1471-2407
PURE UUID: a59211af-83af-4cd9-b985-bd49477c5702
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Date deposited: 07 Apr 2006
Last modified: 16 Mar 2024 02:58
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Contributors
Author:
Martins Kalejs
Author:
Andrey Ivanov
Author:
Gregory Plakhins
Author:
Dzintars Emzinsh
Author:
Timothy M. Illidge
Author:
Jekaterina Erenpreisa
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