Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells
- Latvian Biomedical Research and Study Centre, Riga, LV-1067 (Latvia)
- Paterson Institute of Cancer Research, Manchester University, M20 4BX (United Kingdom)
- Beatson Institute, Glasgow Centre for Cancer Research, Glasgow University, G61 4LG (United Kingdom)
- Latvian Institute of Organic Synthesis, Riga, LV-1006 (Latvia)
- Inst. fuer Radiobiologie der Bundeswehr in Verbindung mit der Univ. Ulm, Munich (Germany)
- Cancer Sciences Division, Southampton University School of Medicine, General Hospital, Southampton SO16 6YD (United Kingdom)
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.
- OSTI ID:
- 22209890
- Journal Information:
- Experimental Cell Research, Vol. 316, Issue 13; Other Information: Copyright (c) 2010 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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