Abstract: For analysis of multidrug resistance, a major barrier to effective cancer chemotherapy, we profiled mRNA expression of the 48 known human ABC transporters in 60 diverse cancer cell lines (the NCI-60) used by the National Cancer Institute to screen for anticancer activity. The use of real-time RT-PCR avoided artifacts commonly encountered with microarray technologies. By correlating the results with the growth inhibitory profiles of 1,429 candidate anticancer drugs tested against the cells, we identified which transporters are more likely than others to confer resistance to which agents. Unexpectedly, we also found and validated compounds whose activity is potentiated, rather than antagonized, by the MDR1 multidrug transporter. Such compounds may serve as leads for development.
Supplemental Figure S1. Structures of the compounds studied
A: Structures of the 17 candidate MDR1-substrates shown in Table
S6. The structure of the 18th candidate ABCB1 substrate (NSC 652903) was
not available from DTP.
Supplemental Figure S2. Expression of ABCG2 mRNA and protein in the 60 cell lines
mRNA expression values (horizontal bars) are taken from Supplemental
Table S1. Cell lines indicated by black bars were shown to express "considerably
high" protein levels by Western blotting (Imai et al, 2002).
Supplemental Table S1 (Microsoft Excel).(Text).
Expression of ABC transporters in the 60 cell lines.
Supplemental Table S2 (Microsoft Word). Clusters observed after hierarchical agglomerative clustering of cell lines based on expression profiles, with average linkage algorithm and a distance metric of 1-r
Supplemental Table S3 (Microsoft Word). Genes statistically significantly associated with tissues of origin
Supplemental Table S4 (Microsoft Word). Association of selected genes with tissue types
Supplemental Table S6 (Microsoft Word). List of the 130 drug-gene pairs showing significant inverse correlation (p < 0.0001)
Supplemental Table S7 (Microsoft Word). List of the 47 ABC transporter genes, their accession numbers, and the primers used for real-time RT-PCR amplification
Supplemental Table S8 (Microsoft Word).
Correlation of ABCB1 mRNA and protein expression in the 60 cell lines
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