Skip to main content
SpringerLink
Log in

Global Effects of Ras Signaling on the Genetic Program in Mammalian Cells

  • Chapter
RAS Family GTPases

Part of the book series: Proteins and Cell Regulation ((PROR,volume 4))

Abstract

While target genes deregulated by oncogenic Ras signaling were identified in a low-throughput manner in the past, recent expression profiling technologies have permitted transcriptome-wide screening approaches. The number of known deregulated genes has increased substantially, as has the proportion of candidate genes involved in various aspects of Ras-induced transformation. This chapter summarizes the results of gene expression profiling studies based on microarrays and advanced cDNA subtraction procedures

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 179.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 229.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Abdollahi, A., Godwin, A.K., Miller, P.D., Getts, L.A., Schultz, D.C., Taguchi, T., Testa, J.R. and Hamilton, T.C. (1997) Identification of a gene containing zinc-finger motifs based on lost expression in malignantly transformed rat ovarian surface epithelial cells. Cancer Res. 57, 2029-2034.

    PubMed  CAS  Google Scholar 

  • Abdollahi, A., Bao, R. and Hamilton, T.C. (1999) LOT1 is a growth suppressor gene down-regulated by the epidermal growth factor receptor ligands and encodes a nuclear zinc-finger protein. Oncogene 18, 6477-6487.

    PubMed  CAS  Google Scholar 

  • Adams, A.T. and Auersperg, N. (1985) A cell line, ROSE 199, derived from normal rat ovarian surface epithelium. Exp. Cell Biol. 53, 181-188.

    PubMed  CAS  Google Scholar 

  • Agathanggelou, A., Bieche, I., Ahmed-Choudhury, J., Nicke, B., Dammann, R., Baksh, S., Gao, B., Minna, J.D., Downward, J., Maher, E.R. and Latif, F. (2003) Identification of novel gene expression targets for the Ras association domain family 1 (RASSF1A) tumor suppressor gene in non-small cell lung cancer and neuroblastoma. Cancer Res. 63, 5344-5351.

    PubMed  CAS  Google Scholar 

  • Alaiya, A.A., Franzen, B., Fujioka, K., Moberger, B., Schedvins, K., Silfversvard, C., Linder, S. and Auer, G. (1997) Phenotypic analysis of ovarian carcinoma: polypeptide expression in benign, borderline and malignant tumors. Int. J. Cancer 73, 678-683.

    PubMed  CAS  Google Scholar 

  • Alvarez, A.A., Axelrod, J.R., Whitaker, R.S., Isner, P.D., Bentley, R.C., Dodge, R.K. and Rodriguez, G.C. (2001) Thrombospondin-1 expression in epithelial ovarian carcinoma: association with p53 status, tumor angiogenesis, and survival in platinum-treated patients. Gynecol. Oncol. 82, 273-278.

    PubMed  CAS  Google Scholar 

  • Asha, H., Nagy, I., Kovacs, G., Stetson, D., Ando, I. and Dearolf, C.R. (2003) Analysis of Ras-induced overproliferation in Drosophila hemocytes. Genetics 163, 203-215.

    PubMed  CAS  Google Scholar 

  • Auersperg, N., Pan, J., Grove, B.D., Peterson, T., Fisher, J., Maines, B.S., Somasiri, A. and Roskelley, C.D. (1999) E-cadherin induces mesenchymal-to-epithelial transition in human ovarian surface epithelium. Proc. Natl. Acad. Sci. U.S.A. 96, 6249-6254.

    PubMed  CAS  Google Scholar 

  • Augenlicht, L.H., Wahrman, M.Z., Halsey, H., Anderson, L., Taylor, J. and Lipkin, M. (1987) Expression of cloned sequences in biopsies of human colonic tissue and in colonic carcinoma cells induced to differentiate in vitro. Cancer Res. 47, 6017-6021.

    PubMed  CAS  Google Scholar 

  • Baba, I., Shirasawa, S., Iwamoto, R., Okumura, K., Tsunoda, T., Nishioka, M., Fukuyama, K., Yamamoto, K., Mekada, E. and Sasazuki, T. (2000) Involvement of deregulated epiregulin expression in tumorigenesis in vivo through activated Ki-Ras signaling pathway in human colon cancer cells. Cancer Res. 60, 6886-6889.

    PubMed  CAS  Google Scholar 

  • Bar-Sagi, D. and Hall, A. (2000) Ras and Rho GTPases: a family reunion. Cell 103, 227-238.

    PubMed  CAS  Google Scholar 

  • Berns, K., Hijmans, E.M., Mullenders, J., Brummelkamp, T.R., Velds, A., Heimerikx, M., Kerkhoven, R.M., Madiredjo, M., Nijkamp, W., Weigelt, B., Agami, R., Ge, W., Cavet, G., Linsley, P.S., Beijersbergen, R.L. and Bernards, R. (2004) A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428, 431-437.

    PubMed  CAS  Google Scholar 

  • Bos, J.L. (1989) Ras oncogenes in human cancer: a review. Cancer Res. 49, 4682-4689.

    PubMed  CAS  Google Scholar 

  • Boyer, B., Valles, A.M. and Edme, N. (2000) Induction and regulation of epithelial-mesenchymal transitions. Biochem. Pharmacol. 60, 1091-1099.

    PubMed  CAS  Google Scholar 

  • Breier, G., Blum, S., Peli, J., Groot, M., Wild, C., Risau, W. and Reichmann, E. (2002) Transforming growth factor-beta and Ras regulate the VEGF/VEGF-receptor system during tumor angiogenesis. Int. J. Cancer 97, 142-148.

    PubMed  CAS  Google Scholar 

  • Brem, R., Certa, U., Neeb, M., Nair, A.P. and Moroni, C. (2001) Global analysis of differential gene expression after transformation with the v-H-ras oncogene in a murine tumor model. Oncogene 20, 2854-2858.

    PubMed  CAS  Google Scholar 

  • Brown, V., Jin, P., Ceman, S., Darnell, J.C., O’Donnell, W.T., Tenenbaum, S.A., Jin, X., Feng, Y., Wilkinson, K.D., Keene, J.D., Darnell, R.B. and Warren, S.T. (2001) Microarray identification of FMRP-associated brain mRNAs and altered mRNA translational profiles in fragile X syndrome. Cell 107, 477-487.

    PubMed  CAS  Google Scholar 

  • Brummelkamp, T.R., Bernards, R. and Agami, R. (2002) A system for stable expression of short interfering RNAs in mammalian cells. Science 296, 550-553.

    PubMed  CAS  Google Scholar 

  • Brummelkamp, T.R., Nijman, S.M., Dirac, A.M. and Bernards, R. (2003) Loss of the cylindromatosis tumour suppressor inhibits apoptosis by activating NF-kappaB. Nature 424, 797-801.

    PubMed  CAS  Google Scholar 

  • Buess, M., Engler, O., Hirsch, H.H. and Moroni, C. (1999) Search for oncogenic regulators in an autocrine tumor model using differential display PCR: identification of novel candidate genes including the calcium channel mtrp6. Oncogene 18, 1487-1494.

    PubMed  CAS  Google Scholar 

  • Campbell, S.L., Khosravi-Far, R., Rossman, K.L., Clark, G.J. and Der, C.J. (1998) Increasing complexity of Ras signaling. Oncogene 17, 1395-1413.

    PubMed  CAS  Google Scholar 

  • Chung, C.H., Bernard, P.S. and Perou, C.M. (2002) Molecular portraits and the family tree of cancer. Nat. Genet. 32 (Suppl.), 533-540.

    PubMed  CAS  Google Scholar 

  • Churchill, G.A. (2002) Fundamentals of experimental design for cDNA microarrays. Nat. Genet. 32 (Suppl.), 490-495.

    PubMed  CAS  Google Scholar 

  • Contente, S., Kenyon, K., Rimoldi, D. and Friedman, R.M. (1990) Expression of gene rrg is associated with reversion of NIH 3T3 transformed by LTR-c-Ha-ras. Science 249, 796-798.

    PubMed  CAS  Google Scholar 

  • D’Cruz, C.M., Gunther, E.J., Boxer, R.B., Hartman, J.L., Sintasath, L., Moody, S.E., Cox, J.D., Ha, S.I., Belka, G.K., Golant, A., Cardiff, R.D. and Chodosh, L.A. (2001) c-MYC induces mammary tumorigenesis by means of a preferred pathway involving spontaneous Kras2 mutations. Nat. Med. 7, 235-239.

    PubMed  Google Scholar 

  • Dahmane, N., Lee, J., Robins, P., Heller, P. and Altaba, A. (1997) Activation of the transcription factor Gli1 and the Sonic hedgehog signalling pathway in skin tumours. Nature 389, 876-881.

    PubMed  CAS  Google Scholar 

  • Darnell, R.B. (2002) RNA logic in time and space. Cell 110, 545-550.

    PubMed  Google Scholar 

  • Delsal, G., Ruaro, M.E., Philipson, L. and Schneider, C. (1992) The Growth Arrest-Specific Gene, gas1, Is Involved in Growth Suppression. Cell 70, 595-607.

    CAS  Google Scholar 

  • Delsal, G., Collavin, L., Ruaro, M.E., Edomi, P., Saccone, S., Dellavalle, G. and Schneider, C. (1994) Structure, Function, and Chromosome Mapping of the Growth-Suppressing Human Homologue of the Murine Gas1 Gene. Proc. Natl. Acad. Sci. U.S.A. 91, 1848-1852.

    CAS  Google Scholar 

  • Denko, N., Stringer, J., Wani, M. and Stambrook, P. (1995) Mitotic and post mitotic consequences of genomic instability induced by oncogenic Ha-ras. Somat. Cell Mol. Genet. 21, 241-253.

    PubMed  CAS  Google Scholar 

  • Denko, N.C., Giaccia, A.J., Stringer, J.R. and Stambrook, P.J. (1994) The human Ha-ras oncogene induces genomic instability in murine fibroblasts within one cell cycle. Proc. Natl. Acad. Sci. U.S.A. 91, 5124-5128.

    PubMed  CAS  Google Scholar 

  • Desai, K.V., Xiao, N., Wang, W., Gangi, L., Greene, J., Powell, J.I., Dickson, R., Furth, P., Hunter, K., Kucherlapati, R., Simon, R., Liu, E.T. and Green, J.E. (2002) Initiating oncogenic event determines gene-expression patterns of human breast cancer models. Proc. Natl. Acad. Sci. U.S.A. 99, 6967-6972.

    PubMed  CAS  Google Scholar 

  • Diatchenko, L., Lau, Y.-F., Campbell, A.P., Chenchik, A., Moqadam, F., Huang, B., Lukyanov, S.A., Lukyanov, K.A., Gurskaya, N.D., Sverdlov, E.D. and Siebert, P.D. (1996) Suppression subtractive hybridization: a method for generating differentially regulated or tissue-specific cDNA probes and libraries. Proc. Natl. Acad. Sci. U.S.A. 93, 6025-6030.

    PubMed  CAS  Google Scholar 

  • Dirac, A.M. and Bernards, R. (2003) Reversal of senescence in mouse fibroblasts through lentiviral suppression of p53. J. Biol. Chem. 278, 11731-11734.

    PubMed  CAS  Google Scholar 

  • Down, T.A. and Hubbard, T.J. (2004) What can we learn from noncoding regions of similarity between genomes? BMC. Bioinformatics 5, 131.

    PubMed  Google Scholar 

  • Dudley, D.T., Pang, L., Decker, S.J., Bridges, A.J. and Saltiel, A.R. (1995) A synthetic inhibitor of the mitogen-activated protein kinase cascade. Proc. Natl. Acad. Sci. U.S.A. 92, 7686-7689.

    PubMed  CAS  Google Scholar 

  • Elbashir, S.M., Harborth, J., Lendeckel, W., Yalcin, A., Weber, K. and Tuschl, T. (2001) Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 411, 494-498.

    PubMed  CAS  Google Scholar 

  • Evangelou, A., Jindal, S.K., Brown, T.J. and Letarte, M. (2000) Down-regulation of transforming growth factor beta receptors by androgen in ovarian cancer cells. Cancer Res. 60, 929-935.

    PubMed  CAS  Google Scholar 

  • Favata, M.F., Horiuchi, K.Y., Manos, E.J., Daulerio, A.J., Stradley, D.A., Feeser, W.S., Van, D.D., Pitts, W.J., Earl, R.A., Hobbs, F., Copeland, R.A., Magolda, R.L., Scherle, P.A. and Trzaskos, J.M. (1998) Identification of a novel inhibitor of mitogen-activated protein kinase kinase. J. Biol. Chem. 273, 18623-18632.

    PubMed  CAS  Google Scholar 

  • Fensterer, H., Giehl, K., Buchholz, M., Ellenrieder, V., Buck, A., Kestler, H.A., Adler, G., Gierschik, P. and Gress, T.M. (2004) Expression profiling of the influence of RAS mutants on the TGFB1-induced phenotype of the pancreatic cancer cell line PANC-1. Genes Chromosomes Cancer 39, 224-235.

    PubMed  CAS  Google Scholar 

  • Furuya, M., Ishikura, H., Kawarada, Y., Ogawa, Y., Sakuragi, N., Fujimoto, S. and Yoshiki, T. (2000) Expression of matrix metalloproteinases and related tissue inhibitors in the cyst fluids of ovarian mucinous neoplasms. Gynecol. Oncol. 78, 106-112.

    PubMed  CAS  Google Scholar 

  • Gadal, F., Bozic, C., Pillot-Brochet, C., Malinge, S., Wagner, S., Le Cam, A., Buffat, L., Crepin, M. and Iris, F. (2003) Integrated transcriptome analysis of the cellular mechanisms associated with a-ras-dependent malignant transformation of the human breast epithelial MCF7 cell line. Nucleic Acids Res. 31, 5789-5804.

    PubMed  CAS  Google Scholar 

  • Germann, A., Dihlmann, S., Hergenhahn, M., Doeberitz, M.K. and Koesters, R. (2003) Expression profiling of CC531 colon carcinoma cells reveals similar regulation of beta-catenin target genes by both butyrate and aspirin. Int. J. Cancer 20 (106), 187-197.

    Google Scholar 

  • Giampuzzi, M., Botti, G., Cilli, M., Gusmano, R., Borel, A., Sommer, P. and Di Donato, A. (2001) Down-regulation of lysyl oxidase-induced tumorigenic transformation in NRK-49F cells characterized by constitutive activation of ras proto-oncogene. J. Biol. Chem. 276, 29226-29232.

    PubMed  CAS  Google Scholar 

  • Gimona, M., Kazzaz, J.A. and Helfman, D.M. (1996) Forced expression of tropomyosin 2 or 3 in v-Ki-ras-transformed fibroblasts results in distinct phenotypic effects. Proc. Natl. Acad. Sci. U.S.A. 93, 9618-9623.

    PubMed  CAS  Google Scholar 

  • Giunciuglio, D., Culty, M., Fassina, G., Masiello, L., Melchiori, A., Paglialunga, G., Arand, G., Ciardiello, F., Basolo, F. and Thompson, E.W. (1995) Invasive phenotype of MCF10A cells overexpressing c-Ha-ras and c-erbB-2 oncogenes. Int. J. Cancer 63, 815-822.

    PubMed  CAS  Google Scholar 

  • Glück, U., Kwiatkowski, D.J. and Ben-Ze’ev, A. (1993) Suppresion of tumorigenicity in simian virus 40-transformed 3T3 cells transfected with a-actinin cDNA. Proc. Natl. Acad. Sci. U.S.A. 90, 383-387.

    PubMed  Google Scholar 

  • Glück, U. and Benzeev, A. (1994) Modulation of alpha-actinin levels affects cell motility and confers tumorigenicity on 3T3 cells. J. Cell Sci. 107, 1773-1782.

    PubMed  Google Scholar 

  • Golub, T.R., Slonim, D.K., Tamayo, P., Huard, C., Gaasenbeek, M., Mesirov, J.P., Coller, H., Loh, M.L., Downing, J.R., Caligiuri, M.A., Bloomfield, C.D. and Lander, E.S. (1999) Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 286, 531-537.

    PubMed  CAS  Google Scholar 

  • Griegel, S., Traub, O., Willecke, K. and Schäfer, R. (1986) Suppression and re-expression of transformed phenotype in hybrids of Ha-ras1 transformed Rat-1 cells and early passage rat embryo fibroblasts. Int. J. Canc. 38, 697-705.

    CAS  Google Scholar 

  • Grill, C., Gheyas, F., Dayananth, P., Jin, W., Ding, W., Qiu, P., Wang, L., Doll, R.J. and English, J.M. (2004) Analysis of the ERK1,2 transcriptome in mammary epithelial cells. Biochem. J. 381, 635-644.

    PubMed  CAS  Google Scholar 

  • Groudine, M. and Weintraub, H. (1980) Activation of cellular genes by avian RNA tumor viruses. Proc. Natl. Acad. Sci. U.S.A. 77, 5351-5354.

    PubMed  CAS  Google Scholar 

  • Habets, G.G., Knepper, M., Sumortin, J., Choi, Y.J., Sasazuki, T., Shirasawa, S. and Bollag, G. (2001) cDNA array analyses of K-ras-induced gene transcription. Methods Enzymol. 332, 245-260.

    PubMed  CAS  Google Scholar 

  • Hahn, W.C., Counter, C.M., Lundberg, A.S., Beijersbergen, R.L., Brooks, M.W. and Weinberg, R.A. (1999) Creation of human tumour cells with defined genetic elements. Nature 400, 464-468.

    PubMed  CAS  Google Scholar 

  • Hajnal, A., Klemenz, R. and Schäfer, R. (1993a) Suppression of ras-mediated transformation. Differential expression of genes encoding extracellular matrix proteins in normal, transformed and revertant cells. Adv. Enzyme Regul. 33, 267-280.

    CAS  Google Scholar 

  • Hajnal, A., Klemenz, R. and Schäfer, R. (1993b) Upregulation of lysyl oxidase in spontaneous revertants of H-ras transformed rat fibroblasts. Canc. Res. 53, 4670-4675.

    CAS  Google Scholar 

  • Hajnal, A., Klemenz, R. and Schäfer, R. (1994) Subtraction cloning of H-Rev107, a gene specifically expressed in H-ras resistant fibroblasts. Oncogene 9, 479-490.

    PubMed  CAS  Google Scholar 

  • Hanna, E.A., Umhauer, S., Roshong, S.L., Piechocki, M.P., Fernstrom, M.J., Fanning, J.D. and Ruch, R.J. (1999) Gap junctional intercellular communication and connexin43 expression in human ovarian surface epithelial cells and ovarian carcinomas in vivo and in vitro. Carcinogenesis 20, 1369-1373.

    PubMed  CAS  Google Scholar 

  • Huang, E., Ishida, S., Pittman, J., Dressman, H., Bild, A., Kloos, M., D’Amico, M., Pestell, R.G., West, M. and Nevins, J.R. (2003) Gene expression phenotypic models that predict the activity of oncogenic pathways. Nat. Genet. 34, 226-230.

    PubMed  CAS  Google Scholar 

  • Hubank, M. and Schatz, D.G. (1994) Identifying differences in mRNA expression by representational difference analysis of cDNA. Nucleic Acids Res. 22, 5640-5648.

    PubMed  CAS  Google Scholar 

  • Ideker, T., Galitski, T. and Hood, L. (2001) A new approach to decoding life: systems biology. Annu. Rev. Genomics Hum. Genet. 2, 343-372.

    PubMed  CAS  Google Scholar 

  • Imren, S., Kohn, D.B., Shimada, H., Blavier, L. and DeClerck, Y.A. (1996) Overexpression of tissue inhibitor of metalloproteinases-2 retroviral-mediated gene transfer in vivo inhibits tumor growth and invasion. Cancer Res. 56, 2891-2895.

    PubMed  CAS  Google Scholar 

  • Jackson, A.L., Bartz, S.R., Schelter, J., Kobayashi, S.V., Burchard, J., Mao, M., Li, B., Cavet, G. and Linsley, P.S. (2003) Expression profiling reveals off-target gene regulation by RNAi. Nat. Biotechnol. 21, 635-637.

    PubMed  CAS  Google Scholar 

  • Jeay, S., Pianetti, S., Kagan, H.M. and Sonenshein, G.E. (2003) Lysyl oxidase inhibits ras-mediated transformation by preventing activation of NF-kappa B. Mol. Cell. Biol. 23, 2251-2263.

    PubMed  CAS  Google Scholar 

  • Jechlinger, M., Grunert, S., Tamir, I.H., Janda, E., Ludemann, S., Waerner, T., Seither, P., Weith, A., Beug, H. and Kraut, N. (2003) Expression profiling of epithelial plasticity in tumor progression. Oncogene 22, 7155-7169.

    PubMed  CAS  Google Scholar 

  • Jo, H., Cho, Y.J., Zhang, H. and Liang, P. (2001) Differential display analysis of gene expression altered by ras oncogene. Methods Enzymol. 332, 233-244.

    PubMed  CAS  Google Scholar 

  • Johnston, I.M., Spence, H.J., Winnie, J.N., McGarry, L., Vass, J.K., Meagher, L., Stapleton, G. and Ozanne, B.W. (2000) Regulation of a multigenic invasion programme by the transcription factor, AP-1: re-expression of a down-regulated gene, TSC-36, inhibits invasion. Oncogene 19, 5348-5358.

    PubMed  CAS  Google Scholar 

  • Jones, D.L., Petty, J., Hoyle, D.C., Hayes, A., Ragni, E., Popolo, L., Oliver, S.G. and Stateva, L.I. (2003) Transcriptome profiling of a Saccharomyces cerevisiae mutant with a constitutively activated Ras/cAMP pathway. Physiol. Genomics 16, 107-118.

    PubMed  CAS  Google Scholar 

  • Kessler, R., Zacharova, A.A., Laursen, N.B., Kalousek, M. and Klemenz, R. (1999) Attenuated expression of the serum responsive T1 gene in ras transformed fibroblasts due to the inhibition of c-fos gene activity. Oncogene 18, 1733-1744.

    PubMed  CAS  Google Scholar 

  • Kielbasa, S.M., Korbel, J.O., Beule, D., Schuchhardt, J. and Herzel, H. (2001) Combining frequency and positional information to predict transcription factor binding sites. Bioinformatics 17, 1019-1026.

    PubMed  CAS  Google Scholar 

  • Land, H., Parada, L.F. and Weinberg, R.A. (1983) Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature 304, 596-602.

    PubMed  CAS  Google Scholar 

  • Land, H., Chen, A.C., Morgenstern, J.P., Parada, L.F. and Weinberg, R.A. (1986) Behavior of myc and ras oncogenes in transformation of rat embryo fibroblasts. Mol. Cell. Biol. 6, 1917-1925.

    PubMed  CAS  Google Scholar 

  • Lewis, J.E., Jensen, P.J. and Wheelock, M.J. (1994) Cadherin function is required for human keratinocytes to assemble desmosomes and stratify in response to calcium. J. Invest. Dermatol. 102, 870-877.

    PubMed  CAS  Google Scholar 

  • Liang, P. and Pardee, A.B. (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257, 967-971.

    PubMed  CAS  Google Scholar 

  • Liang, P., Averboukh, L., Keyomarsi, K., Sager, R. and Pardee, A.B. (1992) Differential display and cloning of messenger RNAs from human breast cancer versus mammary epithelial cells. Cancer Res. 52, 6966-6968.

    PubMed  CAS  Google Scholar 

  • Liang, P., Averboukh, L., Zhu, W.M. and Pardee, A.B. (1994) Ras activation of genes: Mob-1 as a model. Proc. Natl. Acad. Sci. U.S.A. 91, 12515-12519.

    PubMed  CAS  Google Scholar 

  • Lisitsyn, N. and Wigler, M. (1993) Cloning the Differences Between 2 Complex Genomes. Science 259, 946-951.

    PubMed  CAS  Google Scholar 

  • Liu, J., Yang, G., Thompson-Lanza, J.A., Glassman, A., Hayes, K., Patterson, A., Marquez, R.T. and Auersperg, N., Yu, Y., Hahn, W.C., Mills, G.B. and Bast, R.C. Jr. (2004) A genetically defined model for human ovarian cancer. Cancer Res. 64, 1655-1663.

    PubMed  CAS  Google Scholar 

  • Lombardi, L., Ballinari, D., Bongarzone, I., Migliari, M., Mondellini, P., Traversari, C. and Modina, S. (1990) Ultrastructural cytoskeleton alterations and modification of actin expression in the NIH/3T3 cell line after transformation with Ha-ras-activated oncogene. Cell Motil. Cytoskel. 15, 220-229.

    CAS  Google Scholar 

  • Luo, X.N., Reddy, J.C., Yeyati, P.L., Idris, A.H., Hosono, S., Haber, D.A., Licht, J.D. and Atweh, G.F. (1995) The tumor suppressor gene WT1 inhibits ras-mediated transformation. Oncogene 11, 743-750.

    PubMed  CAS  Google Scholar 

  • MacDonald, T.J., Brown, K.M., LaFleur, B., Peterson, K., Lawlor, C., Chen, Y., Packer, R.J., Cogen, P. and Stephan, D.A. (2001) Expression profiling of medulloblastoma: PDGFRA and the RAS/MAPK pathway as therapeutic targets for metastatic disease. Nat. Genet. 29, 143-152.

    PubMed  CAS  Google Scholar 

  • Majidi, M., Gutkind, J.S. and Lichy, J.H. (2000) Deletion of the COOH terminus converts the ST5 p70 protein from an inhibitor of RAS signaling to an activator with transforming activity in NIH-3T3 cells. J. Biol. Chem. 275, 6560-6565.

    PubMed  CAS  Google Scholar 

  • Malumbres, M. and Pellicer, A. (1998) Ras pathways to cell cycle control and cell transformation. Front. Biosci. 3, 887-912.

    Google Scholar 

  • Mccarthy, S.A., Samuels, M.L., Pritchard, C.A., Abraham, J.A. and McMahon, M. (1995) Rapid induction of heparin-binding epidermal growth factor/diphtheria toxin receptor expression by Raf and Ras oncogenes. Genes Dev. 9, 1953-1964.

    PubMed  CAS  Google Scholar 

  • Mikulits, W., Pradet-Balade, B., Habermann, B., Beug, H., Garcia-Sanz, J.A. and Mullner, E.W. (2000) Isolation of translationally controlled mRNAs by differential screening. FASEB J. 14, 1641-1652.

    PubMed  CAS  Google Scholar 

  • Mok, S.C., Chan, W.Y., Wong, K., Muta, M.G. and Berkowitz, R.S. (1996) SPARC, an extracellular matrix protein with tumor-suppressing activity in human ovarian epithelial cells. Oncogene 12, 1895-1901.

    PubMed  CAS  Google Scholar 

  • Morrison, B.H., Bauer, J.A., Kalvakolanu, D.V. and Lindner, D.J. (2001) Inositol hexakisphosphate kinase 2 mediates growth suppressive and apoptotic effects of interferon-beta in ovarian carcinoma cells. J. Biol. Chem. 276, 24965-24970.

    PubMed  CAS  Google Scholar 

  • Murphy, G.A. and Der, C.J. (2002) Ras-mediated deregulation of gene expression and contribution to oncogenesis. In: Oncogene-Directed Therapies. J.W. Rak, ed. (Totowa NJ: Humana Press), pp. 77-100.

    Google Scholar 

  • Ohnami, S., Aoki, K., Yoshida, K., Ohnami, S., Hatanaka, K., Suzuki, K., Sasaki, H. and Yoshida, T. (2003) Expression profiles of pancreatic cancer cell lines infected with antisense K-ras-expressing adenoviral vector. Biochem. Biophys. Res. Commun. 309, 798-803.

    PubMed  CAS  Google Scholar 

  • Olski, T.M., Noegel, A.A. and Korenbaum, E. (2001) Parvin, a 42 kDa focal adhesion protein, related to the alpha-actinin superfamily. J. Cell Sci. 114, 525-538.

    PubMed  CAS  Google Scholar 

  • Ordway, J.M., Williams, K. and Curran, T. (2004) Transcription repression in oncogenic transformation: common targets of epigenetic repression in cells transformed by Fos, Ras or Dnmt1. Oncogene 23, 3737-3748.

    PubMed  CAS  Google Scholar 

  • Ozaki, T. and Sakiyama, S. (1994) Tumor-Suppressive Activity of N03 Gene Product in v-src- Transformed Rat 3Y1 Fibroblasts. Cancer Res. 54, 646-648.

    PubMed  CAS  Google Scholar 

  • Paddison, P.J. and Hannon, G.J. (2002) RNA interference: the new somatic cell genetics? Cancer Cell 2, 17-23.

    PubMed  CAS  Google Scholar 

  • Paddison, P.J., Caudy, A.A., Bernstein, E., Hannon, G.J. and Conklin, D.S. (2002) Short hairpin RNAs (shRNAs) induce sequence-specific silencing in mammalian cells. Genes Dev. 16, 948-958.

    PubMed  CAS  Google Scholar 

  • Paddison, P.J., Silva, J.M., Conklin, D.S., Schlabach, M., Li, M., Aruleba, S., Balija, V., O’Shaughnessy, A., Gnoj, L., Scobie, K., Chang, K., Westbrook, T., Cleary, M., Sachidanandam, R., McCombie, W.R., Elledge, S.J. and Hannon, G.J. (2004) A resource for large-scale RNA-interference-based screens in mammals. Nature 428, 427-431.

    PubMed  CAS  Google Scholar 

  • Paterson, I.C., Matthews, J.B., Huntley, S., Robinson, C.M., Fahey, M., Parkinson, E.K. and Prime, S.S. (2001) Decreased expression of TGF-beta cell surface receptors during progression of human oral squamous cell carcinoma. J. Pathol. 193, 458-467.

    PubMed  CAS  Google Scholar 

  • Petricoin, E.F. III, Hackett, J.L., Lesko, L.J., Puri, R.K., Gutman, S.I., Chumakov, K., Woodcock, J., Feigal, D.W. Jr., Zoon, K.C. and Sistare, F.D. (2002) Medical applications of microarray technologies: a regulatory science perspective. Nat. Genet. 32 (Suppl.), 474-479.

    PubMed  CAS  Google Scholar 

  • Pinkas, J. and Leder, P. (2002) MEK1 signaling mediates transformation and metastasis of EpH4 mammary epithelial cells independent of an epithelial to mesenchymal transition. Cancer Res. 62, 4781-4790.

    PubMed  CAS  Google Scholar 

  • Platt, K.A., Michaud, J. and Joyner, A.L. (1997) Expression of the mouse Gli and Ptc genes is adjacent to embryonic sources of hedgehog signals suggesting a conservation of pathways between flies and mice. Mech. Dev. 62, 121-135.

    PubMed  CAS  Google Scholar 

  • Pradet-Balade, B., Boulme, F., Beug, H., Mullner, E.W. and Garcia-Sanz, J.A. (2001) Translation control: bridging the gap between genomics and proteomics? Trends Biochem. Sci. 26, 225-229.

    PubMed  CAS  Google Scholar 

  • Quade, K. (1979) Transformation of mammalian cells by avian myelocytomatosis virus and avian erythroblastosis virus. Virology 98, 461-465.

    PubMed  CAS  Google Scholar 

  • Rajasekhar, V.K., Viale, A., Socci, N.D., Wiedmann, M., Hu, X. and Holland, E.C. (2003) Oncogenic Ras and Akt signaling contribute to glioblastoma formation by differential recruitment of existing mRNAs to polysomes. Mol. Cell 12, 889-901.

    PubMed  CAS  Google Scholar 

  • Rajasekhar, V.K. and Holland, E.C. (2004) Postgenomic global analysis of translational control induced by oncogenic signaling. Oncogene 19, 3248-3264.

    Google Scholar 

  • Risse, H.G., Adamkiewicz, J., Wimmel, A. and Schuermann, M. (1998) Transition from SCLC to NSCLC phenotype is accompanied by an increased TRE-binding activity and recruitment of specific AP-1 proteins. Oncogene 16, 3057-3068.

    Google Scholar 

  • Romagnolo, B., Jiang, M., Kiraly, M., Breton, C., Begley, R., Wang, J., Lund, J. and Kim, S.K. (2002) Downstream targets of let-60 Ras in Caenorhabditis elegans. Dev. Biol. 247, 127-136.

    PubMed  CAS  Google Scholar 

  • Ross, P.J., George, M., Cunningham, D., DiStefano, F., Andreyev, H.J., Workman, P. and Clarke, P.A. (2001) Inhibition of Kirsten-ras expression in human colorectal cancer using rationally selected Kirsten-ras antisense oligonucleotides. Mol. Cancer Ther. 1, 29-41.

    PubMed  CAS  Google Scholar 

  • Schäfer, R. (1994) Suppression of ras oncogene-mediated transformation. Rev. Physiol. Biochem. Pharmacol. 124, 29-92.

    PubMed  Google Scholar 

  • Schorge, J.O., Miller, Y.B., Qi, L.J., Muto, M.G., Welch, W.R., Berkowitz, R.S. and Mok, S.C. (2000) Genetic alterations of the WT1 gene in papillary serous carcinoma of the peritoneum. Gynecol. Oncol. 76, 369-372.

    PubMed  CAS  Google Scholar 

  • Schulze, A., Lehmann, K., Jefferies, H.B.J., McMahon, M. and Downward, J. (2001) Analysis of the transcriptional program induced by Raf in epithelial cells. Genes Dev. 15, 981-994.

    PubMed  CAS  Google Scholar 

  • Schulze, A., Nicke, B., Warne, P.H., Tomlinson, S. and Downward, J. (2004) The transcriptional response to Raf activation is almost completely dependent on MEK activity and shows a major autocrine component. Mol. Biol. Cell. 15, 673-685.

    Google Scholar 

  • Sehgal, A., Keener, C., Boynton, A.L., Young, R.F., Vermeulen, S.S., Yonemura, K.S., Kohler, E.P., Aldape, H.C., Simrell, C.R. and Murphy, G.P. (1997a) Characterization of C4-2 as a tumor-suppressor gene in human brain tumors. J. Surg. Oncol. 64, 102-108.

    CAS  Google Scholar 

  • Sehgal, A., Ricks, S., Keener, C., Boynton, A.L., Young, R.F., Vermeulen, S.S., Yonemura, K.S., Kohler, E.P., Aldape, H.C., Simrell, C.R. and Murphy, G.P. (1997b) Cloning, sequence, and developmental expression analysis of C4-2, a potential brain tumor-suppressor gene. J. Surg. Oncol. 65, 249-257.

    CAS  Google Scholar 

  • Serrano, M., Lin, A.W., McCurrach, M.E., Beach, D. and Lowe, S.W. (1997) Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16 INK4a. Cell 88, 593-602.

    PubMed  CAS  Google Scholar 

  • Sers, C., Emenegger, U., Husmann, K., Bucher, K., Andres, A.-C. and Schäfer, R. (1997) Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors. J. Cell. Biol. 136, 935-944.

    PubMed  CAS  Google Scholar 

  • Sers, C., Husmann, K., Nazarenko, I., Reich, S., Wiechen, K., Zhumabayeva, B., Adhikari, P., Schroder, K., Gontarewicz, A. and Sch\"afer, R. (2002) The class II tumour suppressor gene H-REV107-1 is a target of interferon-regulatory factor-1 and is involved in IFNgamma-induced cell death in human ovarian carcinoma cells. Oncogene 21, 2829-2839.

    PubMed  CAS  Google Scholar 

  • Shields, J.M., Pruitt, K., McFall, A., Shaub, A. and Der, C.J. (2000) Understanding Ras: ‘it ain’t over’til it’s over’. Trends Cell Biol. 10, 147-154.

    PubMed  CAS  Google Scholar 

  • Slack, J.L., Parker, M.I., Robinson, V.R. and Bornstein, P. (1992) Regulation of Collagen-I Gene Expression by ras. Mol. Cell Biol. 12, 4714-4723.

    PubMed  CAS  Google Scholar 

  • Sledz, C.A., Holko, M., de Veer, M.J., Silverman, R.H. and Williams, B.R. (2003) Activation of the interferon system by short-interfering RNAs. Nat. Cell Biol. 5, 834-839.

    PubMed  CAS  Google Scholar 

  • Sternberg, P.W. and Han, M. (1998) Genetics of RAS signaling in C. elegans. Trends Genet. 14, 466-472.

    PubMed  CAS  Google Scholar 

  • Sumitomo, K., Kurisaki, A., Yamakawa, N., Tsuchida, K., Shimizu, E., Sone, S. and Sugino, H. (2000) Expression of a TGF-beta1 inducible gene, TSC-36, causes growth inhibition in human lung cancer cell lines. Cancer Lett. 155, 37-46.

    PubMed  CAS  Google Scholar 

  • Tan, P.K., Downey, T.J., Spitznagel, E.L. Jr, Xu, P., Fu, D., Dimitrov, D.S., Lempicki, R.A., Raaka, B.M. and Cam, M.C. (2003) Evaluation of gene expression measurements from commercial microarray platforms. Nucleic Acids Res. 31, 5676-5684.

    PubMed  CAS  Google Scholar 

  • Tchernitsa, O.I., Zuber, J., Sers, C., Brinckmann, R., Britsch, S.K., Adams, V. and Sch\"afer, R. (1999) Gene expression profiling of fibroblasts resistant toward oncogene-mediated transformation reveals preferential transcription of negative growth regulators [In Process Citation]. Oncogene 18, 5448-5454.

    PubMed  CAS  Google Scholar 

  • Tchernitsa, O.I., Sers, C., Zuber, J., Hinzmann, B., Grips, M., Schramme, A., Lund, P., Schwendel, A., Rosenthal, A. and Sch\"afer, R. (2004) Transcriptional basis of KRAS oncogene-mediated cellular transformation in ovarian epithelial cells. Oncogene. 23, 4536-4555.

    PubMed  CAS  Google Scholar 

  • Teramoto, H., Malek, R.L., Behbahani, B., Castellone, M.D., Lee, N.H. and Gutkind, J.S. (2003) Identification of H-Ras, RhoA, Rac1 and Cdc42 responsive genes. Oncogene 22, 2689-2697.

    PubMed  CAS  Google Scholar 

  • Tijsterman, M., Ketting, R.F. and Plasterk, R.H. (2002) The genetics of RNA silencing. Annu. Rev. Genet. 36, 489-519.

    PubMed  CAS  Google Scholar 

  • Travers, H., French, N.S. and Norton, J.D. (1996) Suppression of tumorigenicity in Ras-transformed fibroblasts by alpha 2(I) collagen. Cell Growth Differ. 7, 1353-1360.

    PubMed  CAS  Google Scholar 

  • Tullai, J.W., Schaffer, M.E., Mullenbrock, S., Kasif, S. and Cooper, G.M. (2004) Identification of transcription factor binding sites upstream of human genes regulated by the phosphatidylinositol 3-kinase and MEK/ERK signaling pathways. J. Biol. Chem. 279, 20167-20177.

    PubMed  CAS  Google Scholar 

  • Umhauer, S., Ruch, R.J. and Fanning, J. (2000) Gap junctional intercellular communication and connexin 43 expression in ovarian carcinoma. Am. J. Obstet. Gynecol. 182, 999-1000.

    PubMed  CAS  Google Scholar 

  • van de Vijver, M.J., He, Y.D., van’t Veer, L.J., Dai, H., Hart, A.A., Voskuil, D.W., Schreiber, G.J., Peterse, J.L., Roberts, C., Marton, M.J., Parrish, M., Atsma, D., Witteveen, A., Glas, A., Delahaye, L., van d. V., Bartelink, H., Rodenhuis, S., Rutgers, E.T., Friend, S.H. and Bernards, R. (2002) A gene-expression signature as a predictor of survival in breast cancer. N. Engl. J. Med. 19 (347), 1999-2009.

    Google Scholar 

  • Vasseur, S., Malicet, C., Calvo, E.L., Labrie, C., Berthezene, P., Dagorn, J.C. and Iovanna, J.L. (2003) Gene expression profiling by DNA microarray analysis in mouse embryonic fibroblasts transformed by rasV12 mutated protein and the E1A oncogene. Mol. Cancer 19 (2), 19.

    Google Scholar 

  • Vial, E., Sahai, E. and Marshall, C.J. (2003) ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. Cancer Cell 4, 67-79.

    PubMed  CAS  Google Scholar 

  • Vlahos, C.J., Matter, W.F., Hui, K.Y. and Brown, R.F. (1994) A specific inhibitor of phosphatidylinositol 3-kinase, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one (LY294002). J. Biol. Chem. 269, 5241-5248.

    PubMed  CAS  Google Scholar 

  • Wassarman, D.A., Therrien, M. and Rubin, G.M. (1995) The Ras signaling pathway in Drosophila. Curr. Opin. Genet. Dev. 5, 44-50.

    PubMed  CAS  Google Scholar 

  • West, M., Blanchette, C., Dressman, H., Huang, E., Ishida, S., Spang, R., Zuzan, H., Olson, J.A. Jr, Marks, J.R. and Nevins, J.R. (2001) Predicting the clinical status of human breast cancer by using gene expression profiles. Proc. Natl. Acad. Sci. U.S.A. 98, 11462-11467.

    PubMed  CAS  Google Scholar 

  • White, F.C., Benehacene, A., Scheele, J.S. and Kamps, M. (1997) VEGF mRNA is stabilized by ras and tyrosine kinase oncogenes, as well as by UV radiation – evidence for divergent stabilization pathways. Growth Factors 14, 199-212.

    PubMed  CAS  Google Scholar 

  • Yoon, J.W., Kita, Y., Frank, D.J., Majewski, R.R., Konicek, B.A., Nobrega, M.A., Jacob, H., Walterhouse, D. and Iannaccone, P. (2002) Gene expression profiling leads to identification of GLI1-binding elements in target genes and a role for multiple downstream pathways in GLI1-induced cell transformation. J. Biol. Chem. 277, 5548-5555.

    PubMed  CAS  Google Scholar 

  • Zabrenetzky, V., Harris, C.C., Steeg, P.S. and Roberts, D.D. (1994) Expression of the extracellular matrix molecule thrombospondin inversely correlates with malignant progression in melanoma, lung and breast carcinoma cell lines. Int. J. Cancer 59, 191-195.

    PubMed  CAS  Google Scholar 

  • Zajchowski, D.A., Bartholdi, M.F., Gong, Y., Webster, L., Liu, H.L., Munishkin, A., Beauheim, C., Harvey, S., Ethier, S.P. and Johnson, P.H. (2001) Identification of gene expression profiles that predict the aggressive behavior of breast cancer cells. Cancer Res. 61, 5168-5178.

    PubMed  CAS  Google Scholar 

  • Zhang, R., Averboukh, L., Zhu, W., Zhang, H., Jo, H., Dempsey, P.J., Coffey, R.J., Pardee, A.B. and Liang, P. (1998) Identification of rCop-1, a new member of the CCN protein family, as a negative regulator for cell transformation. Mol. Cell. Biol. 18, 6131-6141.

    PubMed  CAS  Google Scholar 

  • Zong, Q., Schummer, M., Hood, L. and Morris, D.R. (1999) Messenger RNA translation state: the second dimension of high-throughput expression screening. Proc. Natl. Acad. Sci. U.S.A. 96, 10632-10636.

    PubMed  CAS  Google Scholar 

  • Zuber, J., Tchernitsa, O.I., Hinzmann, B., Schmitz, A.-C., Grips, M., Hellriegel, M., Sers, C., Rosenthal, A. and Schäfer, R. (2000) A genome-wide survey of Ras transformation targets. Nature Genet. 24, 144-152.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratories of Molecular Tumor Pathology and of Functional Genomics,Charitè, Universitätsmedizin Berlin, Schumannstr. 20/21, D-10117 Berlin, Germany.

    Reinhold Schäfer, Oleg I. Tchernitsa & Christine Sers

Authors
  1. Reinhold Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Oleg I. Tchernitsa
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Christine Sers
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. University of North Carolina at Chapel Hill, U.S.A

    Channing Der

Rights and permissions

Reprints and permissions

Copyright information

© 2006 Springer

About this chapter

Cite this chapter

Schäfer, R., Tchernitsa, O.I., Sers, C. (2006). Global Effects of Ras Signaling on the Genetic Program in Mammalian Cells. In: Der, C. (eds) RAS Family GTPases. Proteins and Cell Regulation, vol 4. Springer, Dordrecht. https://doi.org/10.1007/1-4020-4708-8_8

Download citation

Publish with us

Policies and ethics

Search

Navigation