Studies of X-irradiated bladder cancer cell lines showing differences in p53 status: absence of a p53-dependent cell cycle checkpoint pathway.
Cell growth arrest is a common response to DNA damage by ionising irradiation and the p53 gene has been shown to play an important role in this mechanism, possibly in a tissue-specific manner. Mutations in the p53 gene are frequent in invasive bladder cancers, which are often treated by radiotherapy. In this paper we have investigated the growth response to X-irradiation of three bladder cancer cell lines with differing p53 status: UCRU-BL-17 overexpresses mutant p53, while UCRU-BL-13 and UCRU-BL-28 contain wt P53. We have also examined the expression of proteins reported to be part of the p53 control pathway in response to irradiation-induced DNA damage. No G1 arrest was detectable in any of the cell lines after ionising irradiation; furthermore, in a downstream event reported to be correlated with p53 function there was no increase in WAF-1 protein levels regardless of p53 status. Rather, ionising irradiation resulted in G2 arrest, but the extent of this was not related to p53 status. p16 levels were also not affected by irradiation. Our results suggest that the UCRU-BL-28 cell line may have a defect in the p53-cell control pathway upstream of p53, while UCRU-BL-13 cells may have a defect downstream between p53 and WAF-1.
Ribeiro
J C
JC
Oncology Research Centre, Prince of Wales Hospital, Randwick, NSW, Australia.
Hanley
J R
JR
Russell
P J
PJ
D002453:Cell Cycle / Q000502:physiology / Q000528:radiation effects; D002455:Cell Division / Q000528:radiation effects; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000235:genetics / Q000528:radiation effects; D016147:Genes, Tumor Suppressor; D016158:Genes, p53; D006801:Humans; D007399:Interphase / Q000502:physiology / Q000528:radiation effects; D009687:Nuclear Proteins / Q000096:biosynthesis / Q000502:physiology*; D015203:Reproducibility of Results; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism / Q000502:physiology* / Q000528:radiation effects*; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D004273:DNA, Neoplasm; D009687:Nuclear Proteins; D016159:Tumor Suppressor Protein p53