Changes in BRCA1 and BRCA2 expression produced by chemotherapeutic agents in human breast cancer cells.
We have investigated the effects of chemotherapeutic agents such as adriamycin (ADR), camptothecin (CPT), mitomycin-C (MYC-C) and methotrexate (MTX) on the regulation of expression of the tumor susceptibility genes (BRCA1 and BRCA2), and the association of cell cycle progression in human breast cancer and normal breast epithelial cells. Results revealed that the mRNA and protein expression levels of BRCA1/2 were reduced by the treatment of chemotherapeutic agents used in the breast cancer cell lines tested, with ADR being the most effective. The regulation of the cell cycle was dose-dependent and low doses of ADR (1.5 microM) induced G2/M phase arrest whereas a late S phase arrest was observed with a higher dose of ADR (15 microM) in both breast cancer cells (MCF-7 and MDA-MB-231) tested. In addition, a negative correlation was observed between BRCA1/2 mRNA and expressions of the proteins with the cell cycle alterations being regulated by chemotherapeutic agents.
Su
Jiangfeng
J
Department of Pharmaceutical Sciences, School of Pharmacy, Temple University, 3307 N. Broad Street, Philadelphia, PA 19140, USA.
Ciftci
Kadriye
K
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000633:toxicity; D019313:BRCA1 Protein / Q000235:genetics*; D024682:BRCA2 Protein / Q000235:genetics*; D001943:Breast Neoplasms; D002166:Camptothecin / Q000494:pharmacology* / Q000633:toxicity; D002453:Cell Cycle; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D005260:Female; D006801:Humans; D008727:Methotrexate / Q000494:pharmacology* / Q000633:toxicity; D016685:Mitomycin / Q000494:pharmacology* / Q000633:toxicity; D012333:RNA, Messenger; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019313:BRCA1 Protein; D024682:BRCA2 Protein; D012333:RNA, Messenger; D016685:Mitomycin; D004317:Doxorubicin; D002166:Camptothecin; D008727:Methotrexate