Show simple item record

dc.contributor.authorSalmina, Kristine
dc.contributor.authorJankevics, Eriks
dc.contributor.authorHuna, Anda
dc.contributor.authorPerminov, Dmitry
dc.contributor.authorRadovica, Ilze
dc.contributor.authorKlymenko, Tetyana
dc.contributor.authorIvanov, Andrei
dc.contributor.authorJascenko, Elina
dc.contributor.authorScherthan, Harry
dc.contributor.authorCragg, Mark S
dc.contributor.authorErenpreisa, Jekaterina
dc.date.accessioned2010-09-18T09:13:10Z
dc.date.available2010-09-18T09:13:10Z
dc.date.issued2010-08-01
dc.identifier.citationUp-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells. 2010, 316 (13):2099-112 Exp Cell Resen
dc.identifier.issn0014-4827
dc.identifier.pmid20457152
dc.identifier.doi10.1016/j.yexcr.2010.04.030
dc.identifier.urihttp://hdl.handle.net/10541/111380
dc.description.abstractWe 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.
dc.language.isoenen
dc.subjectCanceren
dc.subjectTumour Suppressor Protein p53en
dc.subject.meshBlotting, Western
dc.subject.meshCell Proliferation
dc.subject.meshCells, Cultured
dc.subject.meshFemale
dc.subject.meshFlow Cytometry
dc.subject.meshFluorescent Antibody Technique
dc.subject.meshHomeodomain Proteins
dc.subject.meshHumans
dc.subject.meshImmunoenzyme Techniques
dc.subject.meshMutation
dc.subject.meshNeoplasms
dc.subject.meshOctamer Transcription Factor-3
dc.subject.meshPolyploidy
dc.subject.meshRNA, Messenger
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshSOXB1 Transcription Factors
dc.subject.meshTumor Suppressor Protein p53
dc.subject.meshUp-Regulation
dc.titleUp-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells.en
dc.typeArticleen
dc.identifier.eissn1090-2422
dc.contributor.departmentLatvian Biomedical Research and Study Centre, Riga, LV-1067, Latvia. kristine@biomed.lu.lven
dc.identifier.journalExperimental Cell Researchen
html.description.abstractWe 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.


Files in this item

This item appears in the following Collection(s)

Show simple item record