Comparative Promoter Analysis of Doxorubicin Resistance-associated Genes Suggests E47 as a Key Regulatory Element

• Published in: Anticancer research Vol. 26; no. 4B; pp. 2971 - 2976
• Main Authors: ANDRÁS GYÖRFFY, BARNA VÁSÁRHELYI, DOMINIKA SZÖKE, MANFRED DIETEL, TIVADAR TULASSAY, BALÁZS GYÖRFFY
• Format: Journal Article
• Language: English
• Published: Attiki International Institute of Anticancer Research 01-07-2006
• Subjects: Antibiotics, Antineoplastic - pharmacology; Binding Sites; Biological and medical sciences; Cell Line, Tumor; Doxorubicin - pharmacology; Drug Resistance, Neoplasm - genetics; Humans; Medical sciences; Neoplasms - drug therapy; Neoplasms - genetics; Promoter Regions, Genetic; TCF Transcription Factors - genetics; Transcription Factor 7-Like 1 Protein; Tumors; Antineoplastic agent; DNA topoisomerase (ATP-hydrolysing); Treatment resistance; Transcription; Enzyme; Transcription promoter; Enzyme inhibitor; cancer chemoresistance; Malignant tumor; Gene expression; Doxorubicin; anthracycline resistance; Isomerases; Cancerology; Gene; Genetics; Regulatory sequence; Anthracyclins; promoter; Comparative study; Transcription regulation
• ISSN: 0250-7005; 1791-7530

Working under the assumption that up- or down-regulation of genes implicated in chemoresistance may be the result of altered
function of regulatory transcription factors (TF), over-represented TF-binding sites of gene lists previously associated with
doxorubicin resistance were the target of our search. First, a data warehouse was set up containing 52 genes which were present
in at least two gene lists; of those, proximal promoter sequences (1 kb upstream and 0.05 kb downstream of the transcriptional
start sites) could be retrieved from genomic databases for 45 genes using the EZ-Retrieve. The TOUCAN tool MotifScanner, which
searches the TRANSFAC database, was used to detect TF-binding sites (TFBSs) in our set of sequences. The statistics tool of
the Java program TOUCAN was applied to the data with the appropriate expected frequencies file to compare the measured prevalence
to a background model. The most significantly over-represented TFBS was that of E47 (p=0.00024, prevalence: 0.2 vs. background:
8.19E-6). In summary, based on the results of our analysis it is hypothesized that the E47 transcription factor may contribute
to doxorubicin resistance.