Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells
Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells
We have previously documented that transient polyploidy is a potential cell survival strategy underlying the clonogenic re-growth of tumour cells after genotoxic treatment. In an attempt to better define this mechanism, we recently documented the key role of meiotic genes in regulating the DNA repair and return of the endopolyploid tumour cells (ETC) to diploidy through reduction divisions after irradiation.
Here, we studied the role of the pluripotency and self-renewal stem cell genes NANOG, OCT4 and SOX2 in this polyploidy-dependent survival mechanism. In irradiation-resistant p53-mutated lymphoma cell-lines (Namalwa and WI-L2-NS) but not sensitive p53 wild-type counterparts (TK6), low background expression of OCT4 and NANOG was up-regulated by ionising radiation with protein accumulation evident in ETC as detected by OCT4/DNA flow cytometry and immunofluorescence (IF). IF analysis also showed that the ETC generate PML bodies that appear to concentrate OCT4, NANOG and SOX2 proteins, which extend into complex nuclear networks.
These polyploid tumour cells resist apoptosis, overcome cellular senescence and undergo bi- and multi-polar divisions transmitting the up-regulated OCT4, NANOG and SOX2 self-renewal cassette to their descendents. Altogether, our observations indicate that irradiation-induced ETC up-regulate key components of germ-line cells, which potentially facilitate survival and propagation of the tumour cell population.
lymphoma, irradiation, polyploidy, OCT4/NANOG/SOX2, self-renewal, cellular senescence
Salmina, Kristine
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Jankevics, Eriks
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Huna, Anda
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Perminov, Dmitry
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Radovica, Ilze
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Klymenko, Tetyana
b4bad036-c62a-407e-a441-833c76df3aec
Ivanov, Andrey
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Jascenko, Elina
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Cragg, Mark
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Scherthan, Harry
ed4655f8-e9e1-49dd-b614-3bce67ec507c
Erenpreisa, Jekaterina
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10 May 2010
Salmina, Kristine
00a98b4d-8de8-4e78-99f7-a8834851d209
Jankevics, Eriks
6dc46ba7-43da-4fbb-b604-ce63573642bc
Huna, Anda
237bfd00-007b-4f76-a34f-a0cef3e95e36
Perminov, Dmitry
b3f9405f-90c7-44e3-923d-949cb81c210d
Radovica, Ilze
6d678c41-6a64-475f-887c-8b5d05e35267
Klymenko, Tetyana
b4bad036-c62a-407e-a441-833c76df3aec
Ivanov, Andrey
0b43b5f4-c35e-4ee8-9fd6-cffe3bbefb1e
Jascenko, Elina
fc1c132e-0d91-4fa4-a2df-a6caf28a7b1c
Cragg, Mark
ec97f80e-f3c8-49b7-a960-20dff648b78c
Scherthan, Harry
ed4655f8-e9e1-49dd-b614-3bce67ec507c
Erenpreisa, Jekaterina
70b5fecb-7208-431f-bd35-ec498edc0033
Salmina, Kristine, Jankevics, Eriks, Huna, Anda, Perminov, Dmitry, Radovica, Ilze, Klymenko, Tetyana, Ivanov, Andrey, Jascenko, Elina, Cragg, Mark, Scherthan, Harry and Erenpreisa, Jekaterina
(2010)
Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells.
Experimental Cell Research.
(doi:10.1016/j.yexcr.2010.04.030).
Abstract
We have previously documented that transient polyploidy is a potential cell survival strategy underlying the clonogenic re-growth of tumour cells after genotoxic treatment. In an attempt to better define this mechanism, we recently documented the key role of meiotic genes in regulating the DNA repair and return of the endopolyploid tumour cells (ETC) to diploidy through reduction divisions after irradiation.
Here, we studied the role of the pluripotency and self-renewal stem cell genes NANOG, OCT4 and SOX2 in this polyploidy-dependent survival mechanism. In irradiation-resistant p53-mutated lymphoma cell-lines (Namalwa and WI-L2-NS) but not sensitive p53 wild-type counterparts (TK6), low background expression of OCT4 and NANOG was up-regulated by ionising radiation with protein accumulation evident in ETC as detected by OCT4/DNA flow cytometry and immunofluorescence (IF). IF analysis also showed that the ETC generate PML bodies that appear to concentrate OCT4, NANOG and SOX2 proteins, which extend into complex nuclear networks.
These polyploid tumour cells resist apoptosis, overcome cellular senescence and undergo bi- and multi-polar divisions transmitting the up-regulated OCT4, NANOG and SOX2 self-renewal cassette to their descendents. Altogether, our observations indicate that irradiation-induced ETC up-regulate key components of germ-line cells, which potentially facilitate survival and propagation of the tumour cell population.
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Published date: 10 May 2010
Keywords:
lymphoma, irradiation, polyploidy, OCT4/NANOG/SOX2, self-renewal, cellular senescence
Identifiers
Local EPrints ID: 153585
URI: http://eprints.soton.ac.uk/id/eprint/153585
ISSN: 0014-4827
PURE UUID: 9308f9e8-6caf-49e4-85d2-5f715927bc23
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Date deposited: 20 May 2010 11:35
Last modified: 14 Mar 2024 02:41
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Contributors
Author:
Kristine Salmina
Author:
Eriks Jankevics
Author:
Anda Huna
Author:
Dmitry Perminov
Author:
Ilze Radovica
Author:
Tetyana Klymenko
Author:
Andrey Ivanov
Author:
Elina Jascenko
Author:
Harry Scherthan
Author:
Jekaterina Erenpreisa
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