Salmina K, Jankevics E, Huna A, Perminov D, Radovica I, Klymenko T, Ivanov A, Jascenko E, Scherthan H, Cragg M, Erenpreisa Je. Up-regulation of the embryonic self-renewal network through reversible polyploidy in irradiated p53-mutant tumour cells. Exp Cell Res 2010, 316:2099- 112.
http://www.ncbi.nlm.nih.gov/pubmed/20457152
Kopsavilkums
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.
Erenpreisa Je and Cragg MS. MOS, aneuploidy and the ploidy cycle of cancer cells. Oncogene 2010, 29:5447-451 (invited review).
http://www.ncbi.nlm.nih.gov/pubmed/20676137
Kopsavilkums
After DNA or spindle damage, p53-defective tumor cells undergo a complex cycle of reversible polyploidy. How this process occurs and more importantly, why, has recently become the focus of several research groups, prompting this review in which we discuss two related phenomena that accompany the reversible polyploidy of tumor cells: the induction of meiosis genes such as MOS and the decrease in genomic instability observed during the reversion from polyploidy to para-diploidy. The reversible polyploidy likely provides the means through which the balance between increased chromosome instability (CIN), driving genetic variation and decreased CIN, necessary for perpetuating these malignant clones, is maintained. These concepts are integrated with recent findings that many meiotic and self-renewal genes become activated during reversible polyploidy and lead us to the hypothesis that tumor cell immortality may be achieved through germline-like transmission.
Erenpreisa J et al. Polyploid tumour cells elicit para-diploid progeny through de-polyploidising divisions and autophagic degradation of the waste DNA and cytoplasm. (iesniegts Cell Biol Int)
K. Silina, P. Zayakin, Z. Kalnina, L. Ivanova, I. Meistere, A. Abols, A. Stengrevics, M. Leja, E.M.I. Suso, G. Gaudernack, T. Wex, D. Schadendorf, A. Line. Molecular analysis of serologically identified tumour antigens reveals novel cancer-testis antigens as potential targets for cancer immunotherapy (sagatavots iesniegšanai Cancer Immunology and Immunotherapy)
