Induction of p53 and melanoma cell death is reciprocal with down-regulation of E2F, cyclin D1 and pRB.
Tumor-suppressor-gene products such as p53 and retinoblastoma (Rb) play an important role as negative regulators of cell-cycle progression, which is reciprocally favored by the availability of cyclin D1 and the E2F transcription factor. We now show that UV irradiation of B16 melanoma after prior exposure to the radiation sensitizer, bromodeoxyuridine (BUdR) leads to induction of p53 and DNA fragmentation, and concomitant decreases in Rb, E2F, cyclin D1, and cell viability, with no comparable effects on irradiated unsensitized cells. Our data suggest that over-expression of p53 correlates with down-regulation of E2F, cyclin D1 in inducing apoptosis.
Rieber
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Instituto Venezolano de Investigaciones Científicas, Centro de Microbiología y Biología Celular, Tumor-Cell Biology Laboratory, Caracas, Venzuela. mrieber@pasteur.ivic.ve
Strasberg-Rieber
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M
D000818:Animals; D001973:Bromodeoxyuridine / Q000494:pharmacology; D002352:Carrier Proteins; D002453:Cell Cycle / Q000187:drug effects / Q000528:radiation effects; D018797:Cell Cycle Proteins; D016923:Cell Death / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D019938:Cyclin D1 / Q000096:biosynthesis*; D004249:DNA Damage; D004273:DNA, Neoplasm / Q000187:drug effects / Q000378:metabolism; D004268:DNA-Binding Proteins; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D050684:E2F Transcription Factors; D015972:Gene Expression Regulation, Neoplastic; D008546:Melanoma, Experimental / Q000378:metabolism* / Q000473:pathology* / Q000532:radiotherapy; D051379:Mice; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology; D016160:Retinoblastoma Protein / Q000096:biosynthesis*; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured / Q000528:radiation effects; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis*; D014466:Ultraviolet Rays
C533431:Arid4a protein, mouse; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D011838:Radiation-Sensitizing Agents; D016160:Retinoblastoma Protein; D056465:Retinoblastoma-Binding Protein 1; D050680:Transcription Factor DP1; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D019938:Cyclin D1; D001973:Bromodeoxyuridine