11:10-12:00, Rm 103

Cancer biologyB-17-74Identification of radiation responsive genes in A549 non-small cell lungcancer cellsKyu Jin Choi, Sangwoo BaeLaboratory of modulation of radiobiological responses, Korea Institute of Radiological and MedicalSciences (KIRAMS), Seoul 139-706, KoreaIdentification of genes that modulate radiation sensitivity provides important tools to studycellular responses to ionizing radiation. We combined DNA microarray assay and viabilityassays to identify modulators of radiation sensitivity in A549 lung cancer cells. Upregulatedgenes were selected from microarray and real-time RT-PCR analysisconfirmed RNA expression levels. EXX expression was induced following ionizingirradiation. Depletion of EXX gene increased radiation sensitivity of A549 cells as shownby decreased surviving cell fraction following irradiation in clonogenic assay. Enhancedradiation sensitivity of EXX-depleted cells was attributable to decreased cell proliferationas well as increased apoptotic cell death following irradiation. Thus endogenous functionof EXX in relation to radiation sensitivity might be regulation of cell proliferation and death.This approach to identification of modulators for radiation sensitivity has severaladvantages in terms of functional selectivity, stringency and time. Further analysis of themodulators should find potential use as radiation biomarkers as well as modulators ofcellular radiation responses.B-17-77MEPH is essential for Oncogenic ras-induced transformation andcellular proliferationMi Young Kang and Hong-Beum KimDepartment of Bio-Materials Engineering, Graduate School and DNA Repair Research Center,Chosun University, 375 Seosuk-dong, Gwangju 501-759, KoreaApproximately 20% of tumors contain activating mutations in the RAS family ofoncogenes. Although the oncogenic effect of Ras are well known, downstream targetmolecules of oncogenic Ras, Which is involved in tumorigenesis, are not fully elucidated.In this report, we found that the levels of MEPH mRNA and protein are significantlyincreased in oncogenic H-RasV12-transformed NIH3T3 cells. We found that the abilitiesof cellular proliferation, colony formation in soft agar and aggregation of MEPHexpressing cells were significantly increased as compared with those of empty vectortransfected cells. The abilities of cellular proliferation, colony formation and aggregation ofH-RasV12-transformed NIH3T3 cells were significantly suppressed by transfection ofMEPH siRNA. In addition, MEPH siRNA transfected H-RasV12-transformed cellsexhibited significant reduction of animal tumor growth, angiogenesis and metastasis.These results suggest that MEPH is a novel downstream target protein of oncogenic H-Ras, and oncogenic H-Ras-induce MEPH expression may be important role foroncogenic H-Ras-mediated tumorigenesis.B-17-75The application of iron nanoparticles for magnetic resonance contrastagentsHunho Jo, Kyung-mi Song, Weejeong Jeon, Euiyoung Jeong, Seonghwan Lee,Sungjin Choi, Si Myeong Song, Changill Ban*Department of Chemistry, Pohang University of Science and Technology, KoreaIn the previous work, we have designed a dual-aptamer complex specific to bothprostate-specific membrane antigens (PSMA) (+) and (-) prostate cancer cells. In thecomplex, an A10 RNA aptamer targeting PSMA (+) cells and a DUP-1 peptide aptamerspecific to PSMA (-) cells were conjugated through streptavidin. Doxorubicin loaded ontothe stem region of the A10 aptamer was delivered not only to PSMA (+) cells but toPSMA (-) cells, and eventually induced apoptosis in both types of prostate cancer cells.Cell death was monitored by measuring guanine concentration in cells using differentialpulse voltammetry (DPV), a simple and rapid electrochemical method, and was furtherconfirmed by directly observing cell morphologies cultured on the transparent indium tinoxide (ITO) glass electrode and checking their viabilities using a trypan blue assay. Toinvestigate the in vivo application of the dual-aptamer system, both A10 and DUP-1aptamers were immobilized on the surface of thermally cross-linked superparamagneticiron oxide nanoparticles (TCL-SPION). Selective cell uptakes and effective drug deliveryaction of these probes were verified by Prussian blue staining and trypan blue staining,respectively.B-17-78Regulation of translationally controlled tumor protein expression inlung cancer cellsJung Eun Kim, Mi Hyeon Jeong, Yun Gyu ParkDepartment of Biochemistry, Korea University, College of Medicine, Room 3102 126-1,5-ga,Anam-dong, Sungbuk-gu, Seoul 136-705, KoreaTCTP is highly conserved in various species including yeast, fruit fly, and mammals. Theprotein is known to be involved in various physiological processes. TCTP has beenreported as a gene down-regulated in tumor reversion and a target of tumor reversion. Inour previous study, we found that protein level of TCTP was high in lung cancer tissuesand cell lines compared to normal controls and knocking down TCTP in lung cancer cellsreduced cell proliferation and clonogenicity. However, there is nothing known about howTCTP is highly expressed in tumor cells. To investigate the signaling pathways involvedin the regulation of TCTP expression, we screened the effect of chemical inhibitors on theprotein level of TCTP in lung cancer cells. We found the signalings by EGFR and mTORhad an effect on TCTP expression. Interestingly, TCTP mRNA level was not changed inthe regulation of TCTP expression through these two signaling pathways indicating thatthe (post)translational mechanisms are involved in the TCTP expression dependent onEGFR and mTOR pathways. This study suggests that the signaling pathways of EGFRand mTOR are involved in maintaining a high level of TCTP protein, and inhibition ofthese signaling pathways is probable to reduce cancer cell growth.B-17-76A potential role of TIS21/BTG2/PC3 in chromatin remodeling byregulating Lymphoid Specific Helicase in Lung cancer cellsSanthoshkumar Sundaramoorthy and In Kyoung LimDepartment of Biochemistry and Molecular Biology, Ajou University School of Medicine, San-5Woncheondong Yeongtong-Gu, Suwon 443-721, KoreaTIS21 (TPA inducible sequences 21)/BTG2/PC3 has been known as one of the earlygrowth response genes and isolated from 3T3 fibroblasts treated with TPA. TIS21interacts with protein-arginine N-methyltransferase and acts as a substrate of argininemethyltransferase. BTG2/TIS21 interacts also with murine homolog of yeast CAF1protein, homeoprotein Hoxb9 and hCAF1/hPOP2. Evidences indicate that TIS21 may beinvolved as a transcriptional co-regulator and has a role in chromatin remodeling.Furthermore, BTG2 enhances retinoic acid-induced differentiation by modulating histoneH4 methylation and acetylation. TIS21 expression is predominant in lymphoid tissues andfetal liver, however, the expression is turned off one week after birth. Lymphoid specifichelicase (Lsh), a chromatin remodeling protein named after its discovery from lymphoidcells, is a homologue of SWI/SNF. We hypothesized that TIS21 may have a role inregulating the expression of Lsh. We are going to present the results on the effect ofTIS21 on the expression of Lsh in various cancer cells, and discuss the posttranslationalmodification of histone molecules such as methylation and acetylation in Ad-TIS21infected cells.B-17-79Nuclear receptor associated gene expression signature in primary versussecondary lung tumorsPeninah M. Wairagu, Seungho Lee, Soojeong Kang, Hyun Won Kim, Jong WhanChoi, Byung-Il Yeh and Yangsik JeongDepartment of Biochemistry, Yonsei University Wonju College of Medicine, KoreaMetastasis marks the last stages of cancer progression and understanding the molecularmechanisms which lead to the invasiveness of primary tumors is an active research area.Here we used QPCR to investigate the NR expression in 6 pairs of lung tumors to identifyand understand the NR associated molecular mechanism for lung cancer metastasis.The 6 pairs of lung cancer cell lines include two pairs of normal versus primary tumors,two pairs of primary versus metastatic tumors and two pairs of metastatic tumors from thesame patient. From the QPCR profile, a subset of NRs was shown to have up to 10-folddifference in gene expression between paired cell lines. Of particular interest is PPARγ,whose expression was 12-fold higher in metastatic tumor as compared to the primarytumor. To identify any gene signature correlated to PPARγexpression, we furtheranalyzed the affymetrix U133AB microarray data for the same lung cell line panel.Phospholamban showed highest positive correlation of 0.99 and Aldehydedehydrogenase 1 family member L1, showed highest negative correlation of -0.99.Further studies are required to determine what pathological role altered PPARγgeneexpression plays in the metastatic process and the impact of this difference on thetherapeutic approach to lung cancer.180 Korean Society for Biochemistry and Molecular Biology