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Role of aldo-keto reductases and other doxorubicin pharmacokinetic genes in doxorubicin resistance, DNA binding, and subcellular localization

Allan D Heibein1, Baoqing Guo2, Jason A Sprowl3, David A MacLean14 and Amadeo M Parissenti12345*

Author Affiliations

1 Graduate Program in Biology, Laurentian University, Sudbury, ON, Canada

2 Regional Cancer Program, Sudbury Regional Hospital, Sudbury, ON, P3E 5J1, Canada

3 Graduate Program in Biomolecular Science, Laurentian University, Sudbury, ON, Canada

4 Division of Medical Sciences, Northern Ontario School of Medicine, Sudbury, ON, Canada

5 Divison Of Oncology, Faculty of Medicine, University of Ottawa, Ottawa, Canada

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BMC Cancer 2012, 12:381  doi:10.1186/1471-2407-12-381

Published: 31 August 2012

Additional files

Additional file 1:

Table S1.Genes associated with doxorubicin pharmacokinetics or pharmacodynamics in cancer cells or cardiomyocytes as identified in the PharmGKB knowledgebase. Those genes identical to and related to genes significantly changing expression upon acquisition of doxorubicin resistance in MCF-7 breast tumour cells by microarray analysis (false discovery rate of 0.01) are listed in bold regular font and bold italics font, respectively. The fold change in gene expression is also listed for upregulated (+) or down regulated (−) genes.

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Additional file 2:

Table S2.Over-representation of doxorubicin pharmacokinetic or pharmacodynamic genes in the dataset of genes associated with the acquisition of doxorubicin resistance in MCF-7 breast tumour cells. The p values assessing the significance of this over-representation are depicted in parentheses, with statistically significant p values listed in bold font.

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Additional file 3:

Table S3.Differences in doxorubicin and doxorubicinol DNA binding parameters. DNA binding by doxorubicin or doxorubicinol was compared in an ethidium bromide displacement assay as described in Materials and Methods. The Bmax and Kapp values for doxorubicin and doxorubicinol are listed, along with the p values for significant differences in their binding parameters (p < 0.05).

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Additional file 4:

Table S4.Primers used for measurement of expression of candidate genes involved in doxorubicin hydroxylation by quantitative PCR. Forward and reverse primers recognizing aldo keto-reductases (AKRs) or carbonyl reductases (CRs) are listed, along with the primers for the reference gene RPS28.

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