Repression of cyclin B1 expression after treatment with adriamycin, but not cisplatin in human lung cancer A549 cells.
Most anticancer drugs cause DNA strand breaks and finally induce cell cycle arrest or cell death. To identify genes involved in these effects, we examined gene expression profiles in human lung cancer A549 cells before and after adriamycin treatment, using a cDNA array technique. In this manner, we identified several up- or down-regulated genes in cells undergoing G2 arrest following adriamycin treatment; among them, cyclin B1 expression was dramatically reduced. The reduction in cyclin B1 expression and G2 arrest were also seen after treatment with etoposide and irinotecan. Previous reports have shown that overexpression of p53 represses cyclin B1 transcription. However, cisplatin neither reduced cyclin B1 expression nor induced G2 phase arrest, while it induced a comparable amount of p53 protein. These results suggest that a reduction in cyclin B1 expression plays a role in the mechanism of action of certain anticancer drugs, including adriamycin, which induce G2 arrest in cancer cells.
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Division of Molecular Pharmacology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, 1-37-1 Kami-Ikebukuro, Toshima-ku, Tokyo 170-8455, Japan.
Yamori
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D000970:Antineoplastic Agents / Q000494:pharmacology; D001483:Base Sequence; D016203:CDC2 Protein Kinase / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology*; D019926:Cyclin B / Q000235:genetics* / Q000378:metabolism; D056744:Cyclin B1; D017931:DNA Primers / Q000235:genetics; D015536:Down-Regulation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C534699:CCNB1 protein, human; D019926:Cyclin B; D056744:Cyclin B1; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D004317:Doxorubicin; D016203:CDC2 Protein Kinase; D002945:Cisplatin