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The expression of topoisomerase II alpha mRNA is increased by the minor groove DNA‐binding drug Hoechst 33258 in MCF‐7 breast cancer cells
Author(s) -
Thomsen Kristen M.,
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.21.6.a1032-d
Subject(s) - topoisomerase , microbiology and biotechnology , transfection , dna , biology , mcf 7 , gene , luciferase , cancer cell , cancer , genetics , human breast
Topoisomerase IIá is a gene that plays a critical role in the replication of DNA. Several anti‐tumor chemotherapeutic agents selectively target the topoisomerase IIá protein and promote the death of rapidly dividing tumor cells. In many drug resistant tumors, topoisomerase IIá has been shown to be transcriptionally down regulated. This lowered level of topoisomerase IIá expression has an adverse effect on the chemosensitivity of tumors to anti‐tumor chemotherapeutic agents. In this study, we examined the effect of the DNA minor groove‐binding agent Hoechst 33258 on the expression of topoisomerase IIá mRNA in subconfluent MCF‐7 cell lines. In order to further investigate these results, we will amplify and clone the promoter regions of topoisomerase IIá from both MCF‐7 and human genomic DNA into the luciferase reporter vector pGL3. Transient transfection analysis and sequence comparisons of the promoter regions from both human and monkey genomic DNA will provide additional information as to the role conserved promoter elements have in promoting the up regulation of topoisomerase IIá in response to Hoechst 33258. Results from these studies will help to identify sequence specific promoter elements that can be targeted for modifying the expression of genes known to be influential in the chemosensitivity of cancer cells.