[Embryonal stem cells do not undergo cell cycle arrest upon exposure to damaging factors].
As shown recently (Malashicheva et al., 2000), embryonic teratocarcinoma F9 mouse cells do not stop on the G1/S border after the treatment with agents causing G1 arrest in normal fibroblast cells. Since after a prolonged cultivation in vitro F9 cells could lose some properties characteristic of the stem cells, we studied here the capability of mouse ES cells to undergo cell cycle blocks following gamma-irradiation, adriamycin and PALA treatment as well as upon cultivation in the presence of nocodazol, an inhibitor of spindle assembly. The results obtained show that ES cells, similarly as their tumorigenic derivative F9 cells, do not demonstrate any delay on the G1/S boundary of the cell cycle. Moreover, nocodazol treatment for 48 h leads to accumulation of polyploid cells. Immunoblot experiments reveal a low level of p21/Waf1 expression both in F9 and in ES cells. Interestingly, the content of p21/Waf1 has been found to increase after cell treatment with proteasome inhibitor lactacystin, implying that p21/Waf1 level is regulated by proteasomal degradation. Thus, the p21/Waf1--dependent mechanisms of cell cycle control (checkpoint control) do not function properly in embryonic stem cells.
Malashicheva
A B
AB
Institute of Cytology RAS, St. Petersburg.
Kisliakova
T V
TV
Savatier
P
P
Pospelov
V A
VA
D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D001224:Aspartic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D002460:Cell Line; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D004622:Embryo, Mammalian / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D015739:Nocodazole / Q000494:pharmacology; D010746:Phosphonoacetic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism; D014407:Tumor Cells, Cultured
C493957:Cdkn1a protein, mouse; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; C067713:lactacystin; D001224:Aspartic Acid; C013195:sparfosic acid; D004317:Doxorubicin; D010746:Phosphonoacetic Acid; D015739:Nocodazole; D000111:Acetylcysteine