Visual Universitätsmedizin Mainz

Publikationen von Mitgliedern der Forschergruppe aus dem Zeitraum der 1. Förderperiode (03/2004 - 03/2007)

Teilprojekt 1 -  Dr. Ernesto Bockamp / Dr. Leonid Eshkind

Prawitt, D., Brixel, L., Spangenberg, C., Eshkind, L., Heck, R., Oesch, F., Zabel, B. and Bockamp E. (2004) RNAi knock-down mice: an emerging technology for post-genomic functional genetics. Cytogenet. Genome Res. 105, 412-421

Eger, K., Hermes, M., Uhlemann, K., Rodewald, S., Ortwein, J., Brulport, M., Bauer, A.W., Schormann, W., Lupatsch, F., Schiffer, I.B., Heimerdinger, C.K., Gebhard, S., Spangenberg, C., Prawitt, D., Trost, T., Zabel, B., Sauer, C., Tanner, B., Kolbl, H., Krugel, U., Franke, H., Illes, P., Madaj-Sterba, P., Bockamp, E., Beckers, T. and Hengstler J.G. (2004)  4-Epidoxycycline: an alternative to doxycycline to control gene expression in conditional mouse models.Biochem. Biophys. Res. Commun. 323, 979-986

Bockamp, E., Antunes, C., Maringer, M., Heck, R., Presser, K., Beilke, S., Ohngemach, S., Alt, R., Cross, M., Sprengel, R., Hartwig, U., Kaina, B., Schmitt, S. and Eshkind L. Tetracycline-controlled transgenic targeting from the SCL locus directs conditional expression to erythrocytes, megakaryocytes, granulocytes and c-kit expressing lineage negative hematopoietic cells.Blood  2006 May 4; Epub ahead of print

Teilprojekt 3 - Prof. Dr. Bernd Epe

Flohr-Beckhaus,, C., Trapp, C., Mahler, H.C., Eckert, I., van der Pluijm, I., van der Horst, G.T.J., Tanaka, K., M?nissier de Murcia, J., Kaina B., Klungland, A., and Epe, B.: Arrest of transcription mediated by Parp1 is required for an OGG1-independent global repair of oxidative DNA base modifications, Nucleic Acids Res., under revision

Andersen, S. Heine,T. Sneve,R., König, I., Krokan, H.E., Epe, B., and Nilsen, H. : Incorporation of dUMP into DNA is a major source of spontaneous DNA damage, while excision of uracil is not required for cytotoxicity of fluoropyrimidines in mouse embryonic fibroblasts, Carcinogenesis, 26, 547-555 (2005).

Sossou, M., Flohr-Beckhaus, C., Schulz, I., Epe, B., and Radicella, J.P.: Overexpression of AP endonuclease 1 partially corrects both the defective single-strand break repair and the basal genomic instability in Xrcc1-deficient cells, Nucleic Acids Res., 33, 298-406 (2005)

Hoffmann, S., Spitkovsky, D., Radicella, J.P., Epe, B. and Wiesner, R.J.: Reactive oxygen species derived from the mitochondrial respiratory chain are not responsible for the basal levels of oxidative base modifications observed in nuclear DNA of mammalian cells, Free Radical Biol. Med. 36, 765-773 (2004)

Heine, T., Glatt H. and Epe, B.: Human cytochrome-P450 reductase can act as source of endogenous oxidative DNA damage and genetic instability. Free Radical Biol. Med., 40, 801-807 (2006).

Hoffmann, S., Greinert, R., Volkmer, B. and Epe, B.: Visible light (>395 nm) causes micronuclei formation in mammalian cells without generation of cyclobutane pyrimidine dimers. Mutat. Res., 572, 142-149 (2005).

Teilprojekt 4 - Prof. Dr. Gerhard Fritz

Fritz, G., Kaina, B. (2006) Late activation of stress kinases (SAPK/JNK) by genotoxins requires the      DNA repair proteins DNA-PKcs and CSB. Mol Biol Cell 17, 851-61.

Nuebel, T., Damrot, J., Roos, W.P., Kaina, B., Fritz, G. (2006) Lovastatin protects human endothelial cells from killing by ionizing radiation without impairing induction and repair of DNA     double-strand breaks. Clin Cancer Res 12, 933-9.

Damrot, J., Nuebel, T., Epe, B., Roos, W.P., Kaina, B., Fritz, G. (2006) Lovastatin protects       human endothelial cells from the genotoxic and cytotoxic effects of the anticancer   drugs   doxorubicin and etoposide. British J. Pharmacology 149, 988-997

Fritz, G. (2005) HMG-CoA reductase inhibitors as anticancer drugs (2005) Int. J. Oncology 27, 1401-1409.

Fritz, G., Kaina, B. (2006) Rho GTPases: Promsising cellular targets for novel anticancer durgs.          Current Cancer Drug Targets 6, 561-571.

Nübel, T., Kaina, B., Kleinert, H., Dippold, W., Fritz, G. (2004) Lovastatin inhibits Rho-regulated expression of E-selectin by TNFa and attenuates tumor cell adhesion. FASEB J., 18, 140-142.

Nuebel, T., Kaina, B., Fritz, G. (2004) Ionizing radiation-induced E-selectin expression and tumor         cell adhesion is inhibited by lovastatin and all-trans retinoic acid. Carcinogenesis 25, 1335-1344.

Brozovic, A., Fritz, G., Christmann, M., Zisowsky, J., Jaehde, U., Osmak, M., Kaina, B. (2004) Long-term activation of SAPK/JNK, p38 kinase and fas-L expression by cisplatin is attenuated in human carcinoma cells that acquired drug resistance. Int. J. Cancer 112, 974-985.

Teilprojekt 5 - Prof. Dr. Bernd Kaina / Dr. Wynand Roos

Roos, W., Baumgartner, M. and Kaina, B. (2004) Apoptosis triggered by DNA damage O6-methylguanine in human lymphocytes requires DNA replication and is mediated by p53 and Fas/CD95/Apo-1, Oncogene, 23, 359-367.

Debiak, M., Nikolova, T. and Kaina, B. (2004) Loss of ATM sensitizes against O6-methylguanine triggered apoptosis, SCEs and chromosomal aberrations, DNA    Repair, 3, 359-368.

Kaina, B., Mühlhausen, U., Piee-Staffa, A., Christmann, M., Garcia Boy, R., Rösch, F. and Schirrmacher, R. (2004) Inhibition of O6-methylguanine-DNA methyltransferase by glucose-conjugated inhibitors: comparison with non-conjugated inhibitors and effect on fotemustine and temozolomide-induced cell death, J. Pharmacol. Expt. Therap., 311, 585-593.

Tomicic, M.T., Christmann M., Fabian, K. and Kaina B. (2005) Apaf-1 deficient mouse fibroblasts are resistant to MNNG and MMS-induced apoptotic death without attenuation of Bcl-2 decline. Toxicol. Appl. Pharmacol., 207, 117-122.

Tsaryk, R., K. Fabian, J. Thacker and B. Kaina (2006) XRCC2 deficiency sensitizes cells to apoptosis by MNNG and the alkylating anticancer drugs temozolomide, fotemustine and mafosfamide, Cancer Letters, 239 (2), 305-313.

Hermisson, M., A. Klumpp, W. Wick, J. Wischhusen, G. Nagel, W. Roos, B. Kaina and M. Weller (2006) O6methylguanine-DNA methyltransferase and p53 status predict temozolomide sensitivity in human malignant glioma cells, J. Neurochem., 96, 766-776.

Roos, W.P., L.F.Z. Batista, S. Naumann, W. Wick, M. Weller, C.F.M. Menck and B. Kaina (2006a) Apoptosis in malignant glioma cells triggered by the temozolomide-induced DNA lesion O6-methylguanine, Oncogene, in press (online available).

Roos, W.,M. Christmann, S. Fraser and B. Kaina (2006b) Embryonic stem cells are highly sensitive to O6-methylguanine induced apoptosis due to increased DNA mismatch repair, submitted.

Kaina, B. (2004) Mechanisms and consequences of methylating agent-induced SCEs and chromosomal aberrations: a long road traveled and still a far way to go, Cytogenet. Genome Res., 104, 77-86.

Kaina, B. and W. Roos (2006) Apoptosis induced by DNA-damaging agents, in K.M. Debatin and S. Fulda, Apoptosis and Cancer Therapy, Wiley-VCH Verlag, Weinheim, 799-821.

Christmann, M., G. Fritz and B. Kaina (2006) Induction of DNA repair genes in mammalian cells in response to genotoxic stress, in Lankenau, D., Genome Dynamics and Stability, Springer Verlag Berlin-Heidelberg,  online available.

Kaina, B. and M. Christmann (2006) O6-Methylguanine-DNA methyltransferases (alkyltransferases). In: Ganten (edt), Encyclopedic Reference of Genomic and Proteomics in Molecular Medicine, Springer Verlag, in press.

Kaina, B. and G. Fritz (2006) DNA Damaging Agents. In: Ganten (edt), Encyclopedic Reference of Genomic and Proteomics in Molecular Medicine, Springer Verlag, in press.

Roos, W.P. and B. Kaina (2006) DNA damage-induced cell death by apoptosis, Trends Mol. Medicine, in press.

Efferth, T. and B. Kaina (2006) Chemical Carcinogenesis: Genotoxic and Non-genotoxic Mechanisms. In  H. Greim and R. Snyder (edts), Introduction to Toxicology and Risk Assessment, John Wiley & Sons Ltd., in press.

Teilprojekt 6 - Dr. Beate Köberle

Dies ist ein neues Teilprojekt der FG.

B. Köberle, J.R.W. Masters and R.D. Wood. Sensitivity of testis tumor cell lines to DNA damage is independent of XPA levels. (2006) Manuscript in preparation. ADDIN EN.REFLIST

C. McGurk, M. Cummings, B. Köberle, J.A. Hartley, R.T. Oliver and J.R. Masters. Regulation of DNA repair gene Expression in human cancer cell lines., J. Cell. Biochemistry 97 (2006) 1121-1136.

B. Köberle, V. Roginskaya and R.D. Wood. XPA protein as a limiting factor for nucleotide excision repair and UV sensitivity in human cells. DNA Repair 5 (2006) 641-648.

M. Cummings, K. Higginbottom, C.J. McGurk, O.G.-W. Wong, B. Köberle, T.D. Oliver and J.R. Masters. XPA versus ERCC1 as chemosensitising agents to cisplatin and mitomycin C in prostate cancer cells: Role of ERCC1 in homologous recombination repair, Biochem Pharmacol 72 (2006) 166-175.

C. Welsh, R. Day, C. McGurk, J.R. Masters, R.D. Wood and B. Köberle. Reduced levels of XPA, ERCC1 and XPF DNA repair proteins in testis tumor cell lines, Int J Cancer 110 (2004) 352-361.

Teilprojekt 7 - Dr. Ekkerhart Lausch / Prof. Dr. Bernhard Zabel

Spangenberg C and Lausch EU, Trost TM, Prawitt D, May A, Keppler R, Fees SA, Reutzel D, Bell C, Schmitt S, Schiffer IB, Weber A, Brenner W, Hermes M, Sahin U, Türeci ö, Koelbl H, Hengstler JG, Zabel BU: ERBB2-mediated transcriptional upregulation of the alpha5/beta1 integrin fibronectin receptor promotes tumor cell survival under adverse conditions. Cancer Res 66:3715-25,2006

Hausherr CK, Schiffer IB, Gebhard S, Banic A, Tanner B, Kolbl H, Thoenes E, Beckers T, Spangenberg C, Prawitt D, Trost T, Zabel B, Oesch F, Hermes M, Hengstler JG: Dephosphorylation of p-ERK1/2 in relation to tumor remission after HER-2 and Raf1 blocking therapy in a conditional mouse tumor model. Mol Carcinog 45:302-8,2006

Prawitt D, Enklaar T, Gartner-Rupprecht B, Spangenberg C, Lausch E, Reutzel D, Fees S, Korzon M, Brozek I, Limon J, Housman DE, Pelletier J, Zabel B: Microdeletion and IGF2 loss of imprinting in a cascade causing Beckwith-Wiedemann syndrome with Wilms' tumor. Nat Genet 37:785-6,2005

Trost T.M. and Lausch EU, Fees,S.A., Schmitt.,S., Enklaar,T., Reutzel,D., Brixel,L.R., Schmidtke,P., Maringer,M., Schiffer,I.B., Heimerdinger,C.K., Hengstler,J.G., Fritz,G., Bockamp,E.O., Prawitt,D., Zabel,B.U., Spangenberg,C. Premature senescence is a primary fail-safe mechanism of ERBB2-driven tumorigenesis in breast carcinoma cells. Cancer Res. 65 (3), 840-9, 2005

Mohrmann G, Hengstler JG, Hofmann TG, Endele SU, Lee B, Stelzer C, Zabel B, Brieger J, Hasenclever D, Tanner B, Sagemueller J, Sehouli J, Will H, Winterpacht A: SPOC1, a novel PHD-finger protein: association with residual disease and survival in ovarian cancer. Int J Cancer 116:547-54,2005

Prawitt D, Enklaar T, Gartner-Rupprecht B, Spangenberg C, Oswald M, Lausch E, Schmidtke P, Reutzel D, Fees S, Lucito R, Korzon M, Brozek I, Limon J, Housman DE, Pelletier J, Zabel B: Microdeletion of target sites for insulator protein CTCF in a chromosome 11p15 imprinting center in Beckwith-Wiedemann syndrome and Wilms' tumor. Proc Natl Acad Sci USA 102:4085-90,2005

Eger K, Hermes M, Uhlemann K, Rodewald S, Ortwein J, Brulport M, Bauer AW, Schormann W, Lupatsch F, Schiffer IB, Heimerdinger CK, Gebhard S, Spangenberg C, Prawitt D, Trost T, Zabel B, Sauer C, Tanner B, Kolbl H, Krugel U, Franke H, Illes P, Madaj-Sterba P, Bockamp EO, Beckers T, Hengstler JG: 4-Epidoxycycline: an alternative to doxycycline to control gene expression in conditional mouse models. Biochem Biophys Res Commun 323:979-86,2004

Albrecht S, Hartmann W, Houshdaran F, Koch A, Gartner B, Prawitt D, Zabel BU, Russo P, von Schweinitz D, Pietsch T: Allelic loss but absence of mutations in the polyspecific transporter gene BWR1A on 11p15.5 in hepatoblastoma. Int J Cancer 111:627-32,2004

Prawitt D, Brixel L, Spangenberg C, Eshkind L, Heck R, Oesch F, Zabel B, Bockamp E. RNAi knock-down mice: an emerging technology for post-genomic functional genetics. Cytogenet Genome Res 105:412-21,2004

Teilprojekt 8 - PD. Dr. Martin Schuler

Dies ist ein neues Teilprojekt der FG.

Chipuk JE, Kuwana T, Bouchier-Hayes L, Droin NM, Newmeyer DD, Schuler M, and Green DR. Direct activation of Bax by p53 mediates mitochondrial membrane permeabilization and apoptosis. Science. 2004;303:1010-1014.

Schinzel A, Kaufmann T, Schuler M, Martinalbo J, Grubb D, and Borner C. Conformational control of Bax localization and apoptotic activity by Pro168. J Cell Biol. 2004;164:1021-1032.

Scott CL, Schuler M, Marsden VS, Egle A, Pellegrini M, Nesic D, Gerondakis S, Nutt SL, Green DR, and Strasser A. Apaf-1 and Caspase-9 do not act as tumor suppressors in myc-induced lymphomagenesis or mouse embryo fibroblast transformation. J Cell Biol. 2004;164:89-96.

Huber C, Bobek N, Kuball J, Thaler S, Hoffarth S, Huber C, Theobald M, and Schuler M. Inhibitors of apoptosis confer resistance to tumour suppression by adoptively transplanted cytotoxic T lymphocytes in vitro and in vivo. Cell Death Differ. 2005;12:317-325.

Meiler J, Vaniet E, Guyot M, Hoffarth S, Höhn Y, Huber C, and Schuler M. Sensitisation of drug-resistant lung cancers to protein kinase C-specific inhibitors by targeting pro-apoptotic BAK. 2006 (in revision)

Teilprojekt 9 - Dr. Stefan Wirtz / PD. Dr. Christoph Becker / Prof. Dr. Markus Neurath

Dies ist ein neues Teilprojekt der FG.

Wirtz, S., C. Becker, M.C. Fantini, E.E. Nieuwenhuis, I. Tubbe, P.R. Galle, H.J. Schild, M. Birkenbach, R.S. Blumberg, and M.F. Neurath. 2005. EBV-induced gene 3 transcription is induced by TLR signaling in primary dendritic cells via NF-kappa B activation. J Immunol 174:2814-2824.

Wirtz, S., I. Tubber, P.R. Galle, H.J. Schild, M. Birkenbach, R.S. Blumberg, and M.F. Neurath. Protection from lethal septic peritonitis by neutralizing the biological function of interleukin-27. J Exp Med in press.

Becker, C., M.C. Fantini, S. Wirtz, A. Nikolaev, R. Kiesslich, H.A. Lehr, P.R. Galle, and M.F. Neurath. 2005. In vivo imaging of colitis and colon cancer development in mice using high resolution chromoendoscopy. Gut 54:950-954.

Fantini, M.C., C. Becker, G. Monteleone, F. Pallone, P.R. Galle, and M.F. Neurath. 2004. Cutting edge: TGF-beta induces a regulatory phenotype in CD4+CD25- T cells through Foxp3 induction and down-regulation of Smad7. J Immunol 172:5149-5153.

Fantini, M.C., C. Becker, I. Tubbe, A. Nikolaev, H.A. Lehr, P. Galle, and M.F. Neurath. 2006. Transforming growth factor beta induced FoxP3+ regulatory T cells suppress Th1 mediated experimental colitis. Gut 55:671-680.

Levy, L., and C.S. Hill. 2006. Alterations in components of the TGF-beta superfamily signaling pathways in human cancer. Cytokine Growth Factor Rev 17:41-58.

Becker, C., M.C. Fantini, S. Wirtz, A. Nikolaev, H.A. Lehr, P.R. Galle, S. Rose-John, and M.F. Neurath. 2005. IL-6 signaling promotes tumor growth in colorectal cancer. Cell Cycle 4:217-220.

Becker, C., M.C. Fantini, C. Schramm, H.A. Lehr, S. Wirtz, A. Nikolaev, J. Burg, S. Strand, R. Kiesslich, S. Huber, H. Ito, N. Nishimoto, K. Yoshizaki, T. Kishimoto, P.R. Galle, M. Blessing, S. Rose-John, and M.F. Neurath. 2004. TGF-beta suppresses tumor progression in colon cancer by inhibition of IL-6 trans-signaling. Immunity 21:491-501.

Rose-John, S., and M.F. Neurath. 2004. IL-6 trans-signaling: the heat is on. Immunity 20:2-4.

Schmitz, J., A. Owyang, E. Oldham, Y. Song, E. Murphy, T.K. McClanahan, G. Zurawski, M.

Moshrefi, J. Qin, X. Li, D.M. Gorman, J.F. Bazan, and R.A. Kastelein. 2005. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 23:479-490.