p53-dependent radioresistance in ovarian carcinoma cell lines.
In the present study, we investigated the radiosensitivity profiles of three established human ovarian carcinoma cell lines, PA-1, Caov-3, and SK-OV-3, using the adenosine triphosphate-cell viability assay (ATP-CVA). We have correlated radioresponsiveness with the p53 status and the p53 accumulation after irradiation as well as with the Bcl-2 expression and the growth rate of these cell lines. The p53 status was examined by immunocytochemistry and a functional assay (functional analysis of separated alleles in yeast, FASAY); the p53 accumulation was determined by immunocytochemistry and flow cytometry. Furthermore, the Bcl-2 expression before and after irradiation was examined by immunocytochemistry. PA-1, expressing wild-type p53, showed an unequivocal accumulation of p53 protein following exposure to irradiation. This cell line was found to be strongly sensitive to irradiation. The two p53 mutant cell lines Caov-3 and SK-OV-3 showed radioresistance at different degrees and irradiation did not result in p53 accumulation. None of the cell lines examined expressed Bcl-2 protein and no change was seen after irradiation. Furthermore, the most sensitive cell line to irradiation, PA-1, showed the highest proliferative activity, while Caov-3 and SK-OV-3, the more resistant cell lines, exhibited lower growth rates. Our findings indicate that the presence of p53 protein is a possible determinant for the cytotoxicity induced by irradiation in the investigated ovarian carcinoma cell lines. Bcl-2 expression does not seem to determine the response to irradiation in these cell lines. Additionally, an association between radioresponsiveness and the growth rate is suggested in PA-1, Caov-3, and SK-OV-3.
Concin
N
N
Department of Gynecology and Obstetrics, Molecular Oncology Group, University of Vienna Medical School, Vienna, Austria.
Zeillinger
C
C
Stimpfel
M
M
Schiebel
I
I
Tong
D
D
Wolff
U
U
Reiner
A
A
Leodolter
S
S
Zeillinger
R
R
D004307:Dose-Response Relationship, Radiation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000473:pathology / Q000532:radiotherapy*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis; D011836:Radiation Tolerance; D014407:Tumor Cells, Cultured; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000502:physiology*
D019253:Proto-Oncogene Proteins c-bcl-2; D016159:Tumor Suppressor Protein p53