11:10-12:00, Rm 103

Stem Cells and Cancer Stem Cells, Chemical Genomics (Drug Screening)S1-1Stem / progenitor cells in vessel formation: development and therapeuticpotentialChangwon ParkDepartment of Pharmacology, College of Medicine, Unviersity of Illinois at Chicago, IL, USAFlk1-/- mice display defects in the yolk sac blood islands, blood vessels, and endocardiumand die around E9.5. Vegf+/- embryos also show blood and vessel defects whichphenocopy deficiencies observed in the Flk1-/- embryos. Fate mapping studies havedemonstrated that FLK1+ mesoderm contributes to the cardiovascular system consistingof hematopoietic, endothelial, cardiac and smooth muscle cells. Despite the crucial role ofFLK1+ mesoderm in the generation of the circulatory system, the mechanisms thatregulate FLK1+ mesoderm formation and differentiation are poorly understood. Recently,we have reported that ER71, a novel member of the ETS transcription factor family, isindispensible for the generation of FLK1+ mesoderm, hematopoietic and endothelial cellsduring embryogenesis, as evident by the complete absence of FLK1+ mesoderm, bloodand vessel structures in Er71-/- mice. Over-expression of ER71 was shown to sufficient toinduce the generation of both hematopoietic and endothelial cells from embryonic stemcells. ChIP assay revealed direct binding of ER71 on the promoter of the Flk1 gene,suggesting the important role of the ER71-FLK1 axis. Currently, we are investigatingdetailed functions of ER71 in hematopoietic and endothelial cell specification anddifferentiation.S1-4Yolk sac endoderm precursor cell lines - the ES cells’new siblingsBert BinasStem cell laboratory, Department of Molecular & Life science, Hanyang University, Ansan, KoreaThe inner cell mass (ICM) of mammalian preimplantation embryos harbors the committedprecursors of the extraembryonic endoderm and epiblastic (fetal) cell lineages, whichoriginate from the same lineage switch. The epiblast precursor is now known to berepresented by the well-known embryonic stem (ES) cell lines, but a cell line correlate ofthe extraembryonic endoderm precursor has not been known. From rat blastocysts, werecently isolated a new type of stem cell lines, named extraembryonic endodermprecursor (XENP) cell lines, that turned out to be at least similar to the committedprecursor of the extraembryonic endoderm. We can now derive these stem cell linesrapidly and in clean form. We describe their molecular signature, growth factorrequirements, and differentiation potentials. We show that in vitro, they exhibit lineageplasticity resulting in multilineage somatic differentiation. A picture is emerging in whichXENP cells and ES cells exhibit overlapping and complementary phenotypes andreciprocal lineage plasticity. XENP cells are a promising new model of the ICM-stageextraembryonic endoderm precursor. Research fund source: KOSEFS1-2Molecular and cellular dynamics of brain cancer stem cellHyunggee KimSchool of Life Sciences and Biotechnology, Korea University, Seoul, KoreaEpidermal growth factor receptor (EGFR) signaling regulates proliferation, angiogenesisand acquisition of glioma stem-like cell (GSC) characteristics by inducing an inhibitor ofdifferentiation 3 (ID3) and ID3-regulated cytokines (GRO1, IL6, and IL8) through the AKTmediatedphosphorylation of Smad5. Conversely, bFGF or EGFR inhibitors suppressEGFR-driven p-AKT, p-Smad5, and ID3 induction, which led to accelerated invasivenessin glioma cells and GSCs by derepressing the ID3-dependent inhibition of p27 KIP1 andMMP3 expression. Xenograft tumors and human GBM specimens showed that p-EGFRand ID3 were abundant in GBM tumor cores, whereas bFGF, p27 KIP1 , and MMP3 werepredominantly expressed in normal tissues surrounding the tumor. However, as bFGFconcentration diminishes, EGFR and ID3 were re-expressed in the infiltrated glioma cellscapable of colonizing in adjacent parenchymal tissues. EGFR inhibitors suppresstumorsphere-forming ability of GSCs, but prime GSCs to become more invasive.Together, these results provide evidence that opposing effects of the EGF and bFGFsignaling pathways on ID3 expression regulate the dynamic processes of gliomagenesis:GSC-based tumor initiation, angiogenesis, and diffuse infiltration into surroundingparenchymal tissues.S2-1Small molecules targeting oxygen sensingHo Jeong KwonChemical Genomics National Research Laboratory, Department of Biotechnology, TranslationalResearch Center for Protein Function Control, College of Life Science and Biotechnology, YonseiUniversity, Seoul 120-752, KoreaThe phenotype controlling effects of small molecules have integrated into a new multiandinter-disciplinary strategy, so called chemical genomics and proteomics. Recently, weisolated terpestacin, a new angiogenesis inhibitor, from fungal metabolites and identified acellular binding protein of terpestacin using phage display biopanning analysis.Terpestacin specifically bound to the 13.4kDa subunit (UQCRB) of Complex III in themitochondrial respiratory chain. Reports suggest that reactive oxygen species (ROS)generation at mitochondrial Complex III triggers hypoxia-inducible factor-1 (HIF-1)stabilization during hypoxia. Indeed, terpestacin binding to UQCRB inhibited hypoxiainducedROS generation, subsequently HIF-1 activation and tumor angiogenesis in vivo,without inhibiting mitochondrial respiration. Accordingly, small molecules targetingUQCRB in mitochondrial complex III can suppress tumor angiogenesis without acting asa respiratory poison. As such, we further developed new small molecules that specificallyregulate the function of UQCRB using the smart chemical library designed bypharmacophore-based virtual screening. New insights from these small molecules andtarget proteins in respect to oxygen sensing and their applications toward angiogenesiswill be presented.S1-3Therapeutic application of stem and progenitor cells for ischemicvascular diseasesHyongbum Kim, Hyun-Jai Cho, Sung-Whan Kim, Bianling Liu, Yong Jin Choi,JiYoon Lee, Young-Doug Sohn, Min-Young Lee, Mackenzie A. Houge and YoungsupYoonEmory University, Atlanta, GA, USABone marrow (BM) cells play an important role in physiologic and therapeuticneovascularization. However, it remains unclear whether any specific uncultured BM cellpopulations have higher angiogenic and/or vasculogenic activities. Moreover, there hasbeen controversy regarding vasculogenesis by BM cells. Here we further sought todetermine the comprehensive characteristics of human and mouse BM-derived CD31+cells in terms of the angiogenic and vasculogenic properties. Comprehensive geneexpression analyses revealed that BM-CD31+ cells expressed higher levels of angiogenicgenes than CD31- cells. Conventional endothelial progenitor cells were almost exclusivelyconfined to the CD31+ cell fraction and culture of CD31+ cells gave rise to endothelialcells. Injection of CD31+ cells into ischemic hindlimb induced repair of ischemia,increased expression of angiogenic and chemoattractive factors, and clearly inducedvasculogenesis, which was demonstrated by three-dimensional confocal microscopic andflow cytometric analyses. These data indicate that BM-CD31+ cells represent highlyangiogenic and vasculogenic cells and can be a novel and highly promising source ofcells for cell therapy to treat ischemic diseases.S2-2Chemo-contral of cancer cell growth in diverse aspects; ER-stress, celldivision and mTORKangdong Liu, Yukihiro Asami, Jae Hyuk Jang, Jong Seog Ahn and Bo Yeon KimWorld Class Institute, Chemical Biology Research Center, Korea Research Institute of Bioscienceand Biotechnology, Ochang, Cheongwon 363-883, KoreaWe have recently identified two compounds showing differential antitumor activities,fusarisetin and AE. An acinar morphogenesis inhibitor named fusarisetin, whichpossesses both an unprecedented carbon skeleton and new pentacyclic ring system, hasbeen identified from fungal library. The X-ray structure of fusarisetin and its target proteinswill be demonstrated as well as its inhibition against colony formation and migration ofMDA-MB-231 cells in 3-D matrigel assay system. On the other hand, AE, a naturalcompound from an edible plant, inhibited the mRORC2 (mTOR complex 2) signalingpathway. It inhibited the phosphorylation of Akt at Ser 473 and Thr 638 by binding tomRORC2 and suppressed tumor formation in mice. Collectively with other data, mTORC2seems to play an important role in prostate cancer development and AE suppressesprostate progression by targeting mTORC2. Combination of fusarisetin and AE would bea better efficient way for cancer treatment.70 Korean Society for Biochemistry and Molecular Biology