Differential Display

Theory and Applications
  • Irina Gromova
  • Pavel Gromov
  • Julio E. Celis
Part of the Springer Protocols Handbooks book series (SPH)


Recent data released by the Human Genome Consortium and Celera Genomics estimates that the human genome might contain about 30,000 protein coding genes (1, and references therein), of which about 15‰ are believed to be expressed in any given cell type (see Chapter 42). The set of expressed proteins and the corresponding messenger RNAs, termed the transcriptome, defines the phenotype of a given cell, tissue, as well as the whole organism. The identification of genes that are differentially expressed under various physiological conditions is one of the major challenges in molecular biology today, as it provides an overview of the regulatory changes that take place in health and disease and highlights potential targets for drug discovery and therapeutic intervention (2). Tremendous efforts are generally required to identify those changes, as the population of altered messengers rarely comprises more than 1‰ of the total transcripts. Over the years, a variety of methods for the identification of differentially regulated genes in cells and tissues have been developed. Northern hybridization (3), nuclease protection (4), and subtractive (5) and differential (6) hybridization all have a number of serious drawbacks because they measure only single RNA species at a time and require a relatively large amount of starting material. The latter is particularly significant because rare transcripts, which often represent low-abundant cell cycle regulators, growth factors, and their receptors as well as signal transduction components, might be missed during the analysis.


Polymerase Chain Reaction Amplification Differential Display Ribonuclease Protection Assay Rare Transcript cDNA Band 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. 1.
    Subramanian, G., Adams, M. D., Venter, J. C., Broder, S. (2001) Implications of the human genome for understanding human biology and medicine. JAMA 286, 2296–2307.PubMedGoogle Scholar
  2. 2.
    Gooley, A. A. and Packer, N. H. (1997) The importance of protein co-and post-translational modifications in proteome projects, in Proteome Research: New Frontiers in Functional Genomics (Principles and Practice) (Wilkins, M. R., Williams, K. L., Appel, R. D., and Hochstrasser, D. F., eds.), Springer-Verlag, Berlin, pp. 65–91.Google Scholar
  3. 3.
    Alwine, J. C., Kemp, D. J., and Stark, G. R. (1977) Method for detection of specific RNAs in agarose gels by transfer to diazobenzyloxymethyl-paper and hybridization with DNA probes. Proc. Natl. Acad. Sci. USA 74, 5350–5354.PubMedGoogle Scholar
  4. 4.
    Tymms, M. J. (1995) Quantitative measurement of mRNA using the RNase protection assay, in In vitro Transcription and Translation Protocols (Tymms, M. J., ed.), Humana, Totowa, NJ, pp. 31–46.Google Scholar
  5. 5.
    Zimmermann, C. R., Orr, W. C., Leclerc, R. F., Barnard, E. C., and Timberlake, W. E. (1980) Molecular cloning and selection of genes regulated in Aspergillus development. Cell 21, 709–715.PubMedGoogle Scholar
  6. 6.
    St John, T. P. and Davis, R. W. (1979) Isolation of galactose-inducible DNA sequences from Saccharomyces cerevisiae by differential plaque filter hybridization. Cell 16, 443–452.PubMedGoogle Scholar
  7. 7.
    Liang, P. and Pardee, A. B. (1992) Differential display of eukaryotic messenger RNA by means of the polymerase chain reaction. Science 257, 967–971.PubMedGoogle Scholar
  8. 8.
    Stein, J. and Liang, P. (2002) Differential display technology: a general guide. Cell. Mol. Life. Sci. 59, 1235–1240.PubMedGoogle Scholar
  9. 9.
    Liang, P. (2002) A decade of differential display. Biotechniques 33, 338–346.PubMedGoogle Scholar
  10. 10.
    Matz, M. V. and Lukyanov, S. A. (1998) Different strategies of differential display: areas of application. Nucleic. Acids. Res. 26, 5537–5543.PubMedGoogle Scholar
  11. 11.
    Velculescu, V. E., Zhang, L., Vogelstein, B., and Kinzler, K. W. (1995) Serial analysis of gene expression. Science 270, 484–487.PubMedGoogle Scholar
  12. 12.
    Schena, M., Shalon, D., Davis, R. W., and Brown, P. O. (1995) Quantitative monitoring of gene expression patterns with a complementary DNA microarray. Science 270, 467–470.PubMedGoogle Scholar
  13. 13.
    Lipshutz, R. J., Fodor, S. P., Gingeras, T. R., and Lockhart, D. J. (1999) High density synthetic oligonucleotide arrays. Nature Genet. 21, 20–24.PubMedGoogle Scholar
  14. 14.
    Welsh, J., Chada, K., Dalal, S. S., Cheng, R., Ralph, D., and McClelland, M. (1992) Arbitrarily primed PCR fingerprinting of RNA. Nucleic Acids. Res. 20, 4965–4970.PubMedGoogle Scholar
  15. 15.
    Liang, P., Bauer, D., Averboukh, L., et al. (1995) Analysis of altered gene expression by differential display. Methods Enzymol. 254, 304–321.PubMedGoogle Scholar
  16. 16.
    Welsh, J. and McClelland, M. (1990) Fingerprinting genomes using PCR with arbitrary primers. Nucleic Acids Res. 18, 7213–7218.PubMedGoogle Scholar
  17. 17.
    Bauer, D., Muller, H., Reich, J., et al. (1993) Identification of differentially expressed mRNA species by an improved display technique (DDRT-PCR). Nucleic Acids Res. 21, 4272–4280.PubMedGoogle Scholar
  18. 18.
    McClelland, M. and Welsh, J. (1994) DNA fingerprinting by arbitrarily primed PCR. PCR Methods Applic. 4, S59–S65.Google Scholar
  19. 19.
    Gall, J. G. and Pardue, M. L. (1969) Formation and detection of RNA-DNA hybrid molecules in cytological preparations. Proc. Natl. Acad. Sci. USA 63, 378–383.PubMedGoogle Scholar
  20. 20.
    John, H. A., Birnstiel, M. L., and Jones, K. W. (1969) RNA-DNA hybrids at the cytological level. Nature 223, 582–587.PubMedGoogle Scholar
  21. 21.
    Rohde, M., Hummel, R., Pallisgaard, N., et al. (1997) Identification and cloning of differentially expressed genes by DDRT-PCR, In PCR Cloning Protocols: From Molecular Cloning to Genetic Engineering (White, B. A., ed.), Humana, Totowa, NJ, pp. 419–430.Google Scholar
  22. 22.
    Nakayama, H., Yokoi, H., and Fujita, J. (1992) Quantification of mRNA by non-radioactive RTPCR and CCD imaging system. Nucleic Acids Res. 20, 4939.PubMedGoogle Scholar
  23. 23.
    Breyne, P. and Zabeau, M. (2001) Genome-wide expression analysis of plant cell cycle modulated genes. Curr. Opin. Plant Biol. 4, 136–142.PubMedGoogle Scholar
  24. 24.
    Liang, P., Averboukh, L., and Pardee, A. B. (1993) Distribution and cloning of eukaryotic mRNAs by means of differential display: refinements and optimization. Nucleic Acids Res. 21, 3269–3275.PubMedGoogle Scholar
  25. 25.
    Wan, J. S., Sharp, S. J., Poirier, G. M., et al. (1996) Cloning differentially expressed mRNAs. Nature Biotechnol. 14, 1685–1691.Google Scholar
  26. 26.
    Liang, P. and Pardee, A. B. (1995) Recent advances in differential display. Curr. Opin. Immunol. 7, 274–280.PubMedGoogle Scholar
  27. 27.
    Colonna-Romano, S., Leone, A., and Maresca, B. (1998) Differential Display Reverse Transcription-PCR (DDRT-PCR). Lab Manual, Springer-Verlag, Berlin.Google Scholar
  28. 28.
    Medhurst, A.D., Chambers, D., Gray, J., et al. (2000) Practical aspects of the experimental design for differential display of transcripts obtained from complex tissue, in Differential Display: A Practical Approach (Leslie, R. A. and Robertson, H. A., eds.), Oxford University Press, Oxford, pp. 35–64.Google Scholar
  29. 29.
    Ahmed, F. E. (2002) Molecular techniques for studying gene expression in carcinogenesis. J. Environ. Sci. Health C. Environ: Carcinog. Ecotoxicol. Rev. 20, 77–116.Google Scholar
  30. 30.
    Broude, N. E. (2002) Differential display in the time of microarrays. Expert Rev. Mol. Diagn. 2, 209–216.PubMedGoogle Scholar
  31. 31.
    Matz, M., Usman, N., Shagin, D., Bogdanova, E., and Lukyanov, S. (1997) Ordered differential display: a simple method for systematic comparison of gene expression profiles. Nucleic Acids Res. 25, 2541–2542.PubMedGoogle Scholar
  32. 32.
    Chen, Z. J., Shen, H., and Tew, K. D. (2001) Gene expression profiling using a novel method: amplified differential gene expression (ADGE). Nucleic Acids Res. 29, E46.PubMedGoogle Scholar
  33. 33.
    Sutcliffe, J. G., Foye, P. E., Erlander, M. G., et al. (2000) TOGA: an automated parsing technology for analyzing expression of nearly all genes. Proc. Natl. Acad. Sci. USA 97, 1976–1981.PubMedGoogle Scholar
  34. 34.
    Lo, D., Hilbush, B., and Sutcliffe, J. G. (2001) TOGA analysis of gene expression to accelerate target development. Eur. J. Pharm. Sci. 14, 191–196.PubMedGoogle Scholar
  35. 35.
    Kornmann, B., Preitner, N., Rifat, D., Fleury-Olela, F., and Schibler, U. (2001) Analysis of circadian liver gene expression by ADDER, a highly sensitive method for the display of differentially expressed mRNAs. Nucleic Acids Res. 29, E51–1.PubMedGoogle Scholar
  36. 36.
    Green, C. D., Simons, J. F., Taillon, B. E., and Lewin, D. A. (2001) Open systems: panoramic views of gene expression. J. Immunol. Methods. 250, 67–79.PubMedGoogle Scholar
  37. 37.
    Fischer, A., Saedler, H., and Theissen, G. (1995) Restriction fragment length polymorphism-coupled domain-directed differential display: a highly efficient technique for expression analysis of multigene families. Proc. Natl. Acad. Sci. USA 92, 5331–5335.PubMedGoogle Scholar
  38. 38.
    Stone, B. and Wharton, W. (1994) Targeted RNA fingerprinting: the cloning of differentiallyexpressed cDNA fragments enriched for members of the zinc finger gene family. Nucleic Acids Res. 22, 2612–2618.PubMedGoogle Scholar
  39. 39.
    Tohonen, V., Osterlund, C., and Nordqvist, K. (1998) Testatin: a cystatin-related gene expressed during early testis development. Proc. Natl. Acad. Sci. USA 95, 14208–14213.PubMedGoogle Scholar
  40. 40.
    Chomczynski, P. and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162, 156–159.PubMedGoogle Scholar
  41. 41.
    Raha, S., Ling, M., and Merante, F. (1998) Extraction of total RNA from tissues and cultured cells, in Molecular Biomethods Handbook (Rapley, R. and Walker, J. M., eds.), Humana, Totowa, NJ, 1–8.Google Scholar
  42. 42.
    Bhaya, D., Vaulot, D., Amin, P., Takahashi, A. W., and Grossman, A. R. (2000) Isolation of regulated genes of the cyanobacterium Synechocystis sp. strain PCC 6803 by differential display. J. Bacteriol. 182, 5692–5699.PubMedGoogle Scholar
  43. 43.
    Brzostowicz, P. C., Gibson, K. L., Thomas, S. M., Blasko, M. S., and Rouviere, P. E. (2000) Simultaneous identification of two cyclohexanone oxidation genes from an environmental Brevibacterium isolate using mRNA differential display. J. Bacteriol. 182, 4241–4248.PubMedGoogle Scholar
  44. 44.
    Guimaraes, M.J., Lee, F., Zlotnik, A., McClanahan, T. (1995) Differential display by PCR: novel findings and applications. Nucleic. Acids. Res. 23, 1832–1833.PubMedGoogle Scholar
  45. 45.
    Zhao, S., Ooi, S. L., and Pardee, A. B. (1995) New primer strategy improves precision of differential display. Biotechniques 18, 848–850.Google Scholar
  46. 46.
    Rohrwild, M., Alpan, R. S., Liang, P., and Pardee, A. B. (1995) Inosine-containing primers for mRNA differential display. Trends. Genet. 11, 300.PubMedGoogle Scholar
  47. 47.
    Diachenko, L. B., Ledesma, J., Chenchik, A. A., and Siebert, P. D. (1996) Combining the technique of RNA fingerprinting and differential display to obtain differentially expressed mRNA. Biochem. Biophys. Res. Commun. 219, 824–828.PubMedGoogle Scholar
  48. 48.
    Lukyanov, K., Diatchenko, L., Chenchik, A., et al. (1997) Construction of cDNA libraries from small amounts of total RNA using the suppression PCR effect. Biochem. Biophys. Res. Commun. 230, 285–288.PubMedGoogle Scholar
  49. 49.
    Vos, P., Hogers, R., Bleeker, M., et al. (1995) AFLP: a new technique for DNA fingerprinting. Nucleic Acids Res. 23, 4407–4414.PubMedGoogle Scholar
  50. 50.
    McClelland, M., Mathieu-Daude, F., and Welsh, J. (1995) RNA fingerprinting and differential display using arbitrarily primed PCR. Trends Genet. 11, 242–246.PubMedGoogle Scholar
  51. 51.
    Bertioli, D. J., Schlichter, U. H., Adams, M. J., Burrows, P. R., Steinbiss, H.H., and Antoniw, J. F. (1995) An analysis of differential display shows a strong bias towards high copy number mRNAs. Nucleic Acids Res. 23, 4520–4523.PubMedGoogle Scholar
  52. 52.
    Graf, D., Fisher, A. G., and Merkenschlager, M. (1997) Rational primer design greatly improves differential display-PCR (DD-PCR). Nucleic Acids Res. 25, 2239–2240.PubMedGoogle Scholar
  53. 53.
    Hakvoort, T. B., Leegwater, A. C., Michiels, F. A., Chamuleau, R. A., and Lamers, W. H. (1994) Identification of enriched sequences from a cDNA subtraction-hybridization procedure. Nucleic Acids Res. 22, 878–879.PubMedGoogle Scholar
  54. 54.
    Ariazi, E. A. and Gould, M. N. (1996) Identifying differential gene expression in monoterpenetreated mammary carcinomas using subtractive display. J. Biol. Chem. 271, 29,286–29,294.PubMedGoogle Scholar
  55. 55.
    Fuchs, B., Zhang, K., Bolander, M. E., and Sarkar, G. (2000) Identification of differentially expressed genes by mutually subtracted RNA fingerprinting. Anal. Biochem. 286, 91–98.PubMedGoogle Scholar
  56. 56.
    Gromova, I., Gromov, P., and Celis, J. E. (2001) A novel member of the glycosyltransferase family, beta 3 Gn-T2, highly downregulated in invasive human bladder transitional cell carcinomas. Mol. Carcinog. 32, 61–72.PubMedGoogle Scholar
  57. 57.
    Gromova, I., Gromov, P., and Celis, J. E. (2002) bc10: a novel human bladder cancer-associated protein with a conserved genomic structure downregulated in invasive cancer. Int. J. Cancer 98, 539–546.PubMedGoogle Scholar
  58. 58.
    Sokolov, B. P. and Prockop, D. J. (1994) A rapid and simple PCR-based method for isolation of cDNAs from differentially expressed genes. Nucleic Acids Res. 22, 4009–4015.PubMedGoogle Scholar
  59. 59.
    Lohmann, J., Schickle, H., and Bosch, T. C. (1995) REN display, a rapid and efficient method for nonradioactive differential display and mRNA isolation. Biotechniques 18, 200–202.PubMedGoogle Scholar
  60. 60.
    Ito, T., Kito, K., Adati, N., Mitsui, Y., Hagiwara, H., and Sakaki, Y. (1994) Fluorescent differential display: arbitrarily primed RT-PCR fingerprinting on an automated DNA sequencer. FEBS Lett. 351, 231–236.PubMedGoogle Scholar
  61. 61.
    An, G., Luo, G., Veltri, R. W., and O’Hara, S. M. (1996) Sensitive, nonradioactive differential display method using chemiluminescent detection. Biotechniques 20, 342–346.PubMedGoogle Scholar
  62. 62.
    Li, F., Barnathan, E. S., and Kariko, K. (1994) Rapid method for screening and cloning cDNAs generated in differential mRNA display: application of northern blot for affinity capturing of cDNAs. Nucleic Acids Res. 22, 1764–1765.PubMedGoogle Scholar
  63. 63.
    Mathieu-Daude, F., Cheng, R., Welsh, J., and McClelland, M. (1996) Screening of differentially amplified cDNA products from RNA arbitrarily primed PCR fingerprints using single strand conformation polymorphism (SSCP) gels. Nucleic Acids Res. 24, 1504–1507.PubMedGoogle Scholar
  64. 64.
    Zhao, S., Ooi, S. L., Yang, F. C., and Pardee, A. B. (1996) Three methods for identification of true positive cloned cDNA fragment in differential display. Biotechniques 20, 400–404.PubMedGoogle Scholar
  65. 65.
    Miele, G., MacRae, L., McBride, D., Manson, J., and Clinton, M. (1998) Elimination of false positives generated through PCR re-amplification of differential display cDNA. Biotechniques 25, 138–144.PubMedGoogle Scholar
  66. 66.
    Gromova, I., Gromov, P., and Celis, J. E. (1999) Identification of true differentially expressed mRNAs in a pair of human bladder transitional cell carcinomas using an improved differential display procedure. Electrophoresis 20, 241–248.PubMedGoogle Scholar
  67. 67.
    Callard, D., Lescure, B., and Mazzolini, L. (1994) A method for the elimination of false positives generated by the mRNA differential display technique. Biotechniques 16, 1100–1103.Google Scholar
  68. 68.
    Shoham, N. G., Arad, T., Rosin-Abersfeld, R., Mashiah, P., Gazit, A., and Yaniv, A. (1996) Differential display assay and analysis. Biotechniques 20, 182–184.PubMedGoogle Scholar
  69. 69.
    Liu, C. and Raghothama, K. G. (1996) Practical method for cloning cDNAs generated in an mRNA differential display. Biotechniques 20, 576–580.PubMedGoogle Scholar
  70. 70.
    Wadhwa, R., Duncan, E., Kaul, S. C., and Reddel, R. R. (1996) An effective elimination of false positives isolated from differential display of mRNAs. Mol. Biotechnol. 6, 213–217.PubMedGoogle Scholar
  71. 71.
    Bryant, Z., Subrahmanyan, L., Tworoger, M., et al. (1999) Characterization of differentially expressed genes in purified Drosophila follicle cells: toward a general strategy for cell type-specific developmental analysis. Proc. Natl. Acad. Sci. USA 96, 5559–5564.PubMedGoogle Scholar
  72. 72.
    Wittwer, C.T., Herrmann, M.G., Moss, A.A., Rasmussen, R.P. (1997) Continuous fluorescence monitoring of rapid cycle DNA amplification. Biotechniques 22, 134–138.Google Scholar
  73. 73.
    Israeli, D., Tessler, E., Haupt, Y., et al. (1997) A novel p53-inducible gene, PAG608, encodes a nuclear zinc finger protein whose overexpression promotes apoptosis. EMBO J. 16, 4384–4392.PubMedGoogle Scholar
  74. 74.
    Lehar, S. M., Nacht, M., Jacks, T., Vater, C. A., Chittenden, T., and Guild, B. C. (1996) Identification and cloning of EI24, a gene induced by p53 in etoposide-treated cells. Oncogene 12, 1181–1187.PubMedGoogle Scholar
  75. 75.
    Gu, Z., Flemington, C., Chittenden, T., and Zambetti, G. P. (2000) ei24, a p53 response gene involved in growth suppression and apoptosis. Mol. Cell. Biol. 20, 233–241.PubMedGoogle Scholar
  76. 76.
    Lin, Y., Ma, W., and Benchimol, S. (2000) Pidd a new death-domain-containing protein, is induced by p53 and promotes apoptosis. Nature Genet. 26, 122–127.PubMedGoogle Scholar
  77. 77.
    Okamura, S., Arakawa, H., Tanaka, T., et al. (2001) p53DINP1, a p53-inducible gene, regulates p53-dependent apoptosis. Mol. Cell. 8, 85–94.PubMedGoogle Scholar
  78. 78.
    Lo, P. K., Chen, J. Y., Lo, W. C., et al. (1999) Identification of a novel mouse p53 target gene DDA3. Oncogene 18, 7765–7774.PubMedGoogle Scholar
  79. 79.
    Oda, E., Ohki, R., Murasawa, H., et al. (2000) Noxa, a BH3-only member of the Bcl-2 family and candidate mediator of p53-induced apoptosis. Science 288, 1053–1058.PubMedGoogle Scholar
  80. 80.
    Leng, R. P., Lin, Y., Ma, W., et al. (2003) Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation. Cell 112, 779–791.PubMedGoogle Scholar
  81. 81.
    Zhang, R., Tan, Z., and Liang, P. (2000) Identification of a novel ligand-receptor pair constitutively activated by ras oncogenes. J. Biol. Chem. 275, 24,436–24,443.PubMedGoogle Scholar
  82. 82.
    Wang, M., Tan, Z., Zhang, R., Kotenko, S. V., and Liang, P. (2002) Interleukin 24 (MDA-7/MOB-5) signals through two heterodimeric receptors, IL-22R1/IL-20R2 and IL-20R1/IL-20R2. J. Biol. Chem. 277, 7341–7347.PubMedGoogle Scholar
  83. 83.
    Zhu, Y., Carroll, M., Papa, F. R., Hochstrasser, M., and D’Andrea, A. D. (1996) DUB-1, a deubiquitinating enzyme with growth-suppressing activity. Proc. Natl. Acad. Sci. USA 93, 3275–3279.PubMedGoogle Scholar
  84. 84.
    Sakuma, S., Saya, H., Ijichi, A., and Tofilon, P. J. (1995) Radiation induction of the receptor tyrosine kinase gene Ptk-3 in normal rat astrocytes. Radiat. Res. 143, 1–7.PubMedGoogle Scholar
  85. 85.
    Liu. J., Liu, H., Zhang, X., Gao, P., Wang, J., and Hu, Z., (2002) Identification and characterization of P15RS, a novel P15(INK4b) related gene on G1/S progression. Biochem. Biophys. Res. Commun. 299, 880–885.PubMedGoogle Scholar
  86. 86.
    Nickenig, G., Baudler, S., Muller, C., Werner, C., et al. (2002) Redox-sensitive vascular smooth muscle cell proliferation is mediated by GKLF and Id3 in vitro and in vivo. FASEB J. 16, 1077–1086.PubMedGoogle Scholar
  87. 87.
    Lee, D. W., Zhang, K., Ning, Z. Q., et al. (2000) Proliferation-associated SNF2-like gene (PASG): a SNF2 family member altered in leukemia. Cancer Res. 60, 3612–3622.PubMedGoogle Scholar
  88. 88.
    Wang, S., Nakashima, S., Sakai, H., Numata, O., Fujiu, K., and Nozawa, Y. (1998) Molecular cloning and cell-cycle-dependent expression of a novel NIMA (never-in-mitosis in Aspergillus nidulans)-related protein kinase (TpNrk) in Tetrahymena cells. Biochem. J. 334(Pt. 1), 197–203.PubMedGoogle Scholar
  89. 89.
    Poirier, G. M., Anderson, G., Huvar, A., et al. (1999) Immune-associated nucleotide-1 (IAN-1) is a thymic selection marker and defines a novel gene family conserved in plants. J. Immunol. 163, 4960–4969.PubMedGoogle Scholar
  90. 90.
    Azzoni, L., Kanakaraj, P., Zatsepina, O., and Perussia, B. (1996) IL-12-induced activation of NK and T cells occurs in the absence of immediate-early activation gene expression. J. Immunol. 157, 3235–3241.PubMedGoogle Scholar
  91. 91.
    Ruegg, C. L., Wu, H. Y., Fagnoni, F. F., Engleman, E. G., and Laus, R. (1996) B4B, a novel growth-arrest gene, is expressed by a subset of progenitor/pre-B lymphocytes negative for cytoplasmic mu-chain. J. Immunol. 157, 72–80.PubMedGoogle Scholar
  92. 92.
    Ishaq, M., Zhang, Y. M., and Natarajan, V. (1998) Activation-induced down-regulation of retinoid receptor RXRalpha expression in human T lymphocytes. Role of cell cycle regulation. J. Biol. Chem. 273, 21,210–21,216.PubMedGoogle Scholar
  93. 93.
    Sun, H. B., Zhu, Y. X., Yin, T., Sledge, G., and Yang, Y. C. (1998) MRG1, the product of a melanocyte-specific gene related gene, is a cytokine-inducible transcription factor with transformation activity. Proc. Natl. Acad. Sci. USA 95, 13,555–13,560.PubMedGoogle Scholar
  94. 94.
    Nocentini, G., Giunchi, L., Ronchetti, S., et al. (1997) A new member of the tumor necrosis factor/nerve growth factor receptor family inhibits T cell receptor-induced apoptosis. Proc. Natl. Acad. Sci. USA 94, 62116–6221.Google Scholar
  95. 95.
    Babu, J. S., Sun, T., Xu, L., and Datta, S. K. (2002) B cell stimulatory effects of alpha-enolase that is differentially expressed in NZB mouse B cells. Clin. Immunol. 104, 293–304.PubMedGoogle Scholar
  96. 96.
    Sawitzki, B., Lehmann, M., Vogt, K., et al. (2002) Bag-1 up-regulation in anti-CD4 mAb treated allo-activated T cells confers resistance to apoptosis. Eur. J. Immunol. 32, 800–809.PubMedGoogle Scholar
  97. 97.
    Amson, R. B., Nemani, M., Roperch, J. P., et al. (1996) Isolation of 10 differentially expressed cDNAs in p53-induced apoptosis: activation of the vertebrate homologue of the drosophila seven in absentia gene. Proc. Natl. Acad. Sci. USA 93, 3953–3957.PubMedGoogle Scholar
  98. 98.
    Semizarov, D., Glesne, D., Laouar, A., Schiebel, K., and Huberman, E. (1998) A lineage-specific protein kinase crucial for myeloid maturation. Proc. Natl. Acad. Sci. USA 95, 15,412–15,417.PubMedGoogle Scholar
  99. 99.
    Garcia-Domingo, D., Leonardo, E., Grandien, A., et al. (1999) DIO-1 is a gene involved in onset of apoptosis in vitro, whose misexpression disrupts limb development. Proc. Natl. Acad. Sci. USA 96, 7992–7997.PubMedGoogle Scholar
  100. 100.
    Jin, F. Y., Nathan, C., Radzioch, D., and Ding, A. (1997) Secretory leukocyte protease inhibitor: a macrophage product induced by and antagonistic to bacterial lipopolysaccharide. Cell 88, 417–426.PubMedGoogle Scholar
  101. 101.
    Blaser, C., Kaufmann, M., Muller, C., et al. (1998) Beta-galactoside-binding protein secreted by activated T cells inhibits antigen-induced proliferation of T cells. Eur. J. Immunol. 28, 2311–2319.PubMedGoogle Scholar
  102. 102.
    Xu, D., Chan, W. L., Leung, B. P., et al. (1998) Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. J. Exp. Med. 187, 787–794.PubMedGoogle Scholar
  103. 103.
    Ali, M., Markham, A. F., and Isaacs, J. D. (2001) Application of differential display to immunological research. J. Immunol. Methods 250, 29–43.PubMedGoogle Scholar
  104. 104.
    Cole, K. A., Krizman, D. B., and Emmert-Buck, M. R. (1999) The genetics of cancer-a 3D model. Nature Genet. 21, 38–41.PubMedGoogle Scholar
  105. 105.
    Radford, D. M., Fair, K., Thompson, A.M., et al. (1993) Allelic loss on a chromosome 17 in ductal carcinoma in situ of the breast. Cancer Res. 53, 2947–2949.PubMedGoogle Scholar
  106. 106.
    Shibata, D., Hawes, D., Li, Z. H., Hernandez, A. M., Spruck, C. H., and Nichols, P. W. (1992) Specific genetic analysis of microscopic tissue after selective ultraviolet radiation fractionation and the polymerase chain reaction. Am. J. Pathol. 141, 539–543.PubMedGoogle Scholar
  107. 107.
    Emmert-Buck, M. R., Roth, M. J., Zhuang, Z., et al. (1994) Increased gelatinase A (MMP-2) and cathepsin B activity in invasive tumor regions of human colon cancer samples. Am. J. Pathol. 145, 1285–1290.PubMedGoogle Scholar
  108. 108.
    Zhuang, Z., Roth, M. J., Emmert-Buck, M. R., Lubensky, I. A., Liotta, L. A., and Solomon, D. (1994) Detection of the von Hippel-Lindau gene deletion in cytologic specimens using microdissection and the polymerase chain reaction. Acta Cytol. 38, 671–675.PubMedGoogle Scholar
  109. 109.
    Emmert-Buck, M. R., Bonner, R. F., Smith, P. D., et al. (1996) Laser capture microdissection. Science 274, 998–1001.PubMedGoogle Scholar
  110. 110.
    Fend, F., Quintanilla-Martinez, L., Kumar, S., et al. (1999) Composite low grade B-cell lymphomas with two immunophenotypically distinct cell populations are true biclonal lymphomas. A molecular analysis using laser capture microdissection. Am. J. Pathol. 154, 1857–1866.PubMedGoogle Scholar
  111. 111.
    Schmidt-Kittler, O., Ragg, T., Daskalakis, A., et al. (2003) From latent disseminated cells to overt metastasis: genetic analysis of systemic breast cancer progression. Proc. Natl. Acad. Sci. USA 100, 7737–7742.PubMedGoogle Scholar
  112. 112.
    Murakami, H., Liotta, L., and Star, R. A. (2000) IF-LCM: laser capture microdissection of immunofluorescently defined cells for mRNA analysis rapid communication. Kidney Int. 58, 1346–1353.PubMedGoogle Scholar
  113. 113.
    Jin, L., Thompson, C. A., Qian, X., Kuecker, S. J., Kulig, E., and Lloyd, R. V. (1999) Analysis of anterior pituitary hormone mRNA expression in immunophenotypically characterized single cells after laser capture microdissection. Lab. Invest. 79, 511–512.PubMedGoogle Scholar
  114. 114.
    Lindeman, N., Waltregny, D., Signoretti, S., and Loda, M. (2002) Gene transcript quantitation by real-time RT-PCR in cells selected by immunohistochemistry-laser capture microdissection. Diagn. Mol. Pathol. 11, 187–192.PubMedGoogle Scholar
  115. 115.
    Ghadersohi, A. and Sood, A. K. (2001) Prostate epithelium-derived Ets transcription factor mRNA is overexpressed in human breast tumors and is a candidate breast tumor marker and a breast tumor antigen. Clin. Cancer Res. 7, 2731–2738.PubMedGoogle Scholar
  116. 116.
    Mellick, A. S., Day, C. J., Weinstein, S. R., Griffiths, L. R., and Morrison, N. A. (2002) Differential gene expression in breast cancer cell lines and stroma-tumor differences in microdissected breast cancer biopsies revealed by display array analysis. Int. J. Cancer. 100, 172–180.PubMedGoogle Scholar
  117. 117.
    Chen, L.C., Manjeshwar, S., Lu, Y., et al. (1998) The human homologue for the Caenorhabditis elegans cul-4 gene is amplified and overexpressed in primary breast cancers. Cancer Res. 58, 3677–3683.PubMedGoogle Scholar
  118. 118.
    Nielsen, H. L., Ronnov-Jessen, L., Villadsen, R., and Petersen, O. W. (2002) Identification of EPSTI1, a novel gene induced by epithelial-stromal interaction in human breast cancer. Genomics 79, 703–710.PubMedGoogle Scholar
  119. 119.
    Wang, G. S., Wang, M. W., Wu, B. Y., You, W. D., and Yang, X. Y. (2003) A novel gene, GCRG224, is differentially expressed in human gastric mucosa. World J. Gastroenterol. 9, 30–34.PubMedGoogle Scholar
  120. 120.
    Tran, Y. K., Bogler, O., Gorse, K. M., Wieland, I., Green, M. R., and Newsham, I. F. (1999) A novel member of the NF2/ERM/4.1 superfamily with growth suppressing properties in lung cancer. Cancer Res. 59, 35–43.PubMedGoogle Scholar
  121. 121.
    Manda, R., Kohno, T., Niki, T., et al. (2000) Differential expression of the LAMB3 and LAMC2 genes between small cell and non-small cell lung carcinomas. Biochem. Biophys. Res. Commun. 275, 440–445.PubMedGoogle Scholar
  122. 122.
    Yu, L., Hui-chen, F., Chen, Y., et al. (1999) Differential expression of RAB5A in human lung adenocarcinoma cells with different metastasis potential. Clin. Exp. Metastas. 17, 213–219.Google Scholar
  123. 123.
    Hsu, N. Y., Ho, H. C., Chow, K. C., et al. (2001) Overexpression of dihydrodiol dehydrogenase as a prognostic marker of non-small cell lung cancer. Cancer Res. 61, 2727–2731.PubMedGoogle Scholar
  124. 124.
    Neef, R., Kuske, M. A., Prols, E., and Johnson, J. P. (2002) Identification of the human PHLDA1/TDAG51 gene: down-regulation in metastatic melanoma contributes to apoptosis resistance and growth deregulation. Cancer Res. 62, 5920–5929.PubMedGoogle Scholar
  125. 125.
    Cole, K. A., Chuaqui, R. F., Katz, K., et al. (1998) cDNA sequencing and analysis of POV1 (PB39): a novel gene up-regulated in prostate cancer. Genomics 51, 282–287.PubMedGoogle Scholar
  126. 126.
    King, H. C. and Sinha, A. A. (2001) Gene expression profile analysis by DNA microarrays: promise and pitfalls. JAMA 286, 2280–2288.PubMedGoogle Scholar

Copyright information

© Humana Press Inc., Totowa, NJ 2005

Authors and Affiliations

  • Irina Gromova
    • 1
  • Pavel Gromov
    • 1
  • Julio E. Celis
    • 1
  1. 1.Department of Proteomics in Cancer, Institute of Cancer BiologyThe Danish Cancer SocietyCopenhagenDenmark

Personalised recommendations