Figure 1
Ganetespib resistance and correlating expression levels of UGT1A in CRC-derived cell lines and primary tumors. (a) The growth inhibitory concentration of ganetespib was determined for 11 cell lines derived from CRC (blue columns), as detailed in Supplementary Figure S1. The corresponding expression levels of pan-UGT1A, initially found to correlate with ganetespib resistance through microarray analysis (Supplementary Table S1), were re-determined by reverse transcription and quantitative PCR (red columns). Correlation between ganetespib resistance and UGT1A expression levels was highly significant (R=0.976). (b) UGT1A protein levels were determined by immunoblot analysis for the same cell lines as in (a), to show that ganetespib-resistant cell lines have high levels of UGT1A protein. GAPDH detection serves as a loading control. (c) To analyze the distribution of UGT1A mRNA expression levels in primary colorectal tumors, microarray hybridization data sets from 217 rectal carcinomas were obtained.28, 29 The mean hybridization intensities from three probes corresponding to UGT1A (log2 scale) were normalized according to their deviation from the overall mean intensity of all tumors. The distribution of UGT1A levels was determined in the same way for 11 CRC cell lines.25 Overlay of both distributions reveals that tumors and cell lines display similar variations of UGT1A expression
