Regulation of BRCA1 and BRCA2 transcript in response to cisplatin, adriamycin, taxol and ionising radiation is correlated to p53 functional status in ovarian cancer cell lines.
Recent studies suggest that BRCA1 and BRCA2 expression, in response to cytotoxic agents, may be dependent on p53 status. To investigate this possibility, we quantified their transcripts in ovarian cancer cells, PA1 (wild-type p53), CaOV-3 (mutated p53) and SKOV-3 (null p53) exposed to four cytotoxic agents. In PA1, taxol and cisplatin had no effect, while adriamycin and ionising radiation (IR) induced both genes. In SKOV-3, expression decreased in response to taxol and cisplatin, and initially decreased then increased in response to adriamycin while IR had no effect. CaOV-3 responded similarly to SKOV-3, except for both genes being increased by cisplatin. We speculate that this regulation may be part of the survival response to certain cytotoxic agents and may be dependent in part on p53 status of cells.
Aunoble
B
B
Laboratoire d'Oncologie Moleculaire, Centre Jean Perrin, BP 392, 63011 Clermont-Ferrand, France.
Bernard-Gallon
D
D
Bignon
Y J
YJ
D000970:Antineoplastic Agents / Q000494:pharmacology*; D019313:BRCA1 Protein / Q000096:biosynthesis / Q000235:genetics*; D024682:BRCA2 Protein; D002945:Cisplatin / Q000494:pharmacology; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000494:pharmacology; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000528:radiation effects*; D006801:Humans; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D017239:Paclitaxel / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D011839:Radiation, Ionizing; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism*; D014466:Ultraviolet Rays
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D017931:DNA Primers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D004317:Doxorubicin; D017239:Paclitaxel; D002945:Cisplatin