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The minor groove binding drug berenil up‐regulates the expression of topoisomerase II alpha in developing zebrafish
Author(s) -
Edwards Curtis,
Daggett Melissa A. F.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a290
Subject(s) - topoisomerase , biology , microbiology and biotechnology , dna , zebrafish , dna replication , embryo , gene , genetics
Topoisomerase II alpha relieves supercoiling in the DNA double helix during DNA replication. Topoisomerase II alpha is normally up‐regulated in rapidly proliferating cells. Minor groove binding drugs (MGBDs), such as Hoechst 33258, can down‐regulate the expression of topoisomerase II alpha in cancer cells grown in culture by interfering with transcription factor binding at specific A/T rich sequences in the topoisomerase II alpha promoter. These results have indicated a clinical role for MGBDs in regulating topoisomerase II alpha during cancer therapy. In this study, we have examined the effects of the MGBD berenil, on the expression of topoisomerase II alpha in the rapidly dividing cells of zebrafish embryos. Semi‐quantitative PCR analysis of topoisomerase II alpha expression in 24 hour embryos exposed to berenil indicated an up‐regulation of topoisomerase II alpha compared to the unexposed control embryos. These results merit further analysis of the effects of MGBDs, such as berenil, on topoisomerase II alpha expression in intact organisms as opposed to isolated cells in culture. Further characterization of berenil on cells in intact embryos including its effects on cell proliferation, differential gene expression, and overall development of the zebrafish embryo will be presented.