title: Changes in gene expression induced by Sp1 knockdown differ from those caused by challenging Sp1 binding to gene promoters.
abstract: C/G-rich DNA regions, which include those recognized by the Sp1 transcription factor in several gene promoters, also encompass potential binding sites for the DNA-intercalating anthracyclines doxorubicin and WP631. We explored the differences between changes in gene expression caused by the ability of these drugs to compete with Sp1 for binding to DNA and those produced by Sp1 knockdown. By quantitative RT-PCR of around 100 genes, most of them involved in control of cell cycle progression, we found that the treatment of human MDA-MB231 breast carcinoma cells with bis-anthracycline WP631 for 24 h produced a profile of gene down-regulation markedly different from the profile caused by doxorubicin treatment or by stable Sp1 knockdown. These observations are rationalized by considering a near-specific effect of WP631 on Sp1 interaction with several gene promoters, thus representing potential therapeutic targets for WP631, in contrast to a less specific effect of reducing the availability of Sp1 through RNA interference. Genes down-regulated upon each treatment were mapped to their molecular and biological functions, which documented the down-regulation, among other things, of genes involved in mRNA transcription regulation, granting us insights into the effects of challenging the transactivation of gene expression by Sp1.
authors.affiliation: Instituto de Biología Molecular de Barcelona, CSIC, Parc Cientific de Barcelona, E-08028 Barcelona, Spain.
authors.forename: Sylvia
authors.initials: S
authors.lastname: Mansilla
authors.forename: Waldemar
authors.initials: W
authors.lastname: Priebe
authors.forename: José
authors.initials: J
authors.lastname: Portugal
mesh_terms: D000903:Antibiotics, Antineoplastic / Q000494:pharmacology; D045744:Cell Line, Tumor; D003630:Daunorubicin / Q000031:analogs & derivatives / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D005786:Gene Expression Regulation; D055785:Gene Knockdown Techniques; D006801:Humans; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics; D020218:Response Elements / Q000502:physiology*; D014158:Transcription, Genetic / Q000187:drug effects / Q000502:physiology*; D015533:Transcriptional Activation / Q000502:physiology*
chemical_list: D000903:Antibiotics, Antineoplastic; D012333:RNA, Messenger; C104426:WP 631; D004317:Doxorubicin; D003630:Daunorubicin