STANDARD_NAME MARTINEZ_RESPONSE_TO_TRABECTEDIN SYSTEMATIC_NAME M5077 COLLECTION C2:CGP MSIGDB_URL https://www.gsea-msigdb.org/gsea/msigdb/human/geneset/MARTINEZ_RESPONSE_TO_TRABECTEDIN NAMESPACE AFFY_HuGene DESCRIPTION_BRIEF Genes down-regulated by trabectedin [PubChem=3199] and its synthetic analog phthalascidin Pt 650 in HCT116 cells (colon cancer). DESCRIPTION_FULL BACKGROUND: Ecteinascidin 743 (Et 743) is a potent antitumor marine alkaloid currently undergoing phase II clinical trials. The synthetic analog phthalascidin (Pt 650), a designed structural analog of Et 743 displays in vitro potency comparable to Et 743. In this study, we used a panel of 36 human cancer cell lines, flow cytometry and oligonucleotide microarrays to analyze further these two compounds in a parallel fashion with regard to both antitumor activity (phenotype) and gene expression (genotype) bases. RESULTS: The cancer panel experiment established that activity patterns of Et 743 and Pt 650 were essentially the same with their IC(50) values ranging from pM to low nM. By means of flow cytometric cell cycle analysis using HCT116 cells, they were shown to disrupt S phase progression after a 12-h treatment at 2.0 nM, eventually resulting in the late S and G2/M accumulation at the 24-h time point. Array-based gene expression monitoring also demonstrated that the Et 743 and Pt 650 profiles were highly similar in two distinct cancer cell lines, HCT116 colon and MDA-MB-435 breast. Characteristic changes were observed in subsets of genes involved in DNA damage response, transcription and signal transduction. In HCT116 carrying the wild-type p53 tumor suppressor gene, the up-regulation of several p53-responsive genes was evident. Furthermore, a subset of genes encoding DNA-binding proteins to specific promoter regions (e.g. the CCAAT box) was down-regulated in both cell lines, suggesting one potential mode of action of this series of antitumor agents. CONCLUSION: A combination of gene expression analysis using oligonucleotide microarrays and flow cytometry confirms an earlier finding that Et 743 and Pt 650 have remarkably similar biological activities. PMID 11755394 GEOID AUTHORS Martinez EJ,Corey EJ,Owa T CONTRIBUTOR John Newman CONTRIBUTOR_ORG University of Washington EXACT_SOURCE Table 1A FILTERED_BY_SIMILARITY EXTERNAL_NAMES_FOR_SIMILAR_TERMS EXTERNAL_DETAILS_URL SOURCE_MEMBERS AF005887_at,D16688_s_at,D26070_at,D50857_at,D63480_at,D79994_at,D85433_at,D87446_at,HG2167-HT2237_at,HG3075-HT3236_s_at,HG3342-HT3519_s_at,HG511-HT511_at,L07956_at,L13744_at,L32832_s_at,L38608_at,L38616_at,L40393_at,L40904_at,L77886_at,M29971_at,M74099_at,M83233_at,M83822_at,M97675_at,S62539_at,S72904_at,S78825_at,S79219_s_at,S79639_at,U22055_at,U26424_at,U28042_at,U28749_s_at,U30999_at,U33936_s_at,U37146_at,U40038_at,U40622_at,U43944_at,U46116_at,U49957_s_at,U50078_at,U50196_at,U59919_at,U68019_at,U79260_at,U83115_at,U84388_at,U88666_at,U90902_at,U90916_at,U91931_at,U95740_rna1_at,X06745_at,X99050_rna1_at,Z34918_at GENE_SYMBOLS ATF6,MLLT3,ITPR1,DOCK1,SPIDR,KANK1,COMMD1,TMEM131,,,,,GBE1,MLLT3,ZFHX3,ALCAM,BABAM2,NUMB,PPARG,PTPRK,MGMT,CUX1,TCF12,LRBA,ROR1,IRS1,ENOX2,ID1,PCCA,EXT1,SND1,STK3,DDX10,HMGA2,ALCAM,ADK,NCOR2,GNAQ,XRCC4,ME1,PTPRG,LPP,HERC1,ADK,KIFAP3,SMAD3,FTO,CRYBG1,CRADD,SRPK2,TIAM1,SORL1,AP3B1,MARF1,POLA1,UVRAG,EIF4G3 FOUNDER_NAMES