Analysis of p53-dependent mechanisms in the maintenance of genetic stability in diploid tumourigenic line SK-UT-1B of human uterine leiomyosarcoma.
The cells of tumourigenic line SK-UT-1B combine features characteristic both of normal (diploid karyotype, a low level of polyploid cells, absence of chromosomal marker) and tumour cells (high level of chromosomal instability, high malignancy). We suggest that maintenance of diploid karyotype in this line is controlled via the p53/p21 pathway. We demonstrate that the amount of p53 increases following gamma-irradiation and accumulated p53 protein seems to be functional as p53-luc and p21/Waf-luc reporter plasmids were found to be activated. However, gamma-irradiation-induced increase of p53 was not accompanied by increase of p21/Waf on the protein level. Apparently this is one of the reasons for G1/S and G2/M checkpoint control disruption. The absence of these checkpoints could not prevent the proliferation of cells with intrachromosomal rearrangements. The only effective checkpoint in SK-UT-1B is the p53-dependent M checkpoint, which directed the cells with changed chromosome numbers to apoptosis and therefore strictly guarded the diploidy of the cell population. This indicates that p53 can control the preservation of genetic stability at different levels via different pathways.
Smirnova
I S
IS
Institute of Cytology, Russian Academy of Science, St Petersburg. smir@mail.cytspb.rssi.ru
Yakovleva
T K
TK
Rosanov
Y M
YM
Aksenov
N D
ND
Pospelova
T V
TV
D017209:Apoptosis / Q000235:genetics* / Q000528:radiation effects; D002453:Cell Cycle / Q000235:genetics; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins / Q000235:genetics; D004249:DNA Damage / Q000235:genetics / Q000528:radiation effects; D004171:Diploidy; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D007621:Karyotyping; D007890:Leiomyosarcoma / Q000235:genetics* / Q000473:pathology; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000528:radiation effects; D014594:Uterine Neoplasms / Q000235:genetics* / Q000473:pathology
C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D016213:Cyclins; D016159:Tumor Suppressor Protein p53