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  • Oncogenomics
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Identification of Src transformation fingerprint in human colon cancer

Oncogene volume 21, pages 7256–7265 (2002)Cite this article

Abstract

We used a classical rodent model of transformation to understand the transcriptional processes, and hence the molecular and cellular events a given cell undergoes when progressing from a normal to a transformed phenotype. Src activation is evident in 80% of human colon cancer, yet the myriad of cellular processes effected at the level of gene expression has yet to be fully documented. We identified a Src ‘transformation fingerprint’ within the gene expression profiles of Src-transformed rat 3Y1 fibroblasts demonstrating a progression in transformation characteristics. To evaluate the role of this gene set in human cancer development and progression, we extracted the orthologous genes present on the Affymetrix Hu95A GeneChip™ (12k named genes) and compared expression profiles between the Src-induced rodent cell line model of transformation and staged colon tumors where Src is known to be activated. A similar gene expression pattern between the cell line model and staged colon tumors for components of the cell cycle, cytoskeletal associated proteins, transcription factors and lysosomal proteins suggests the need for co-regulation of several cellular processes in the progression of cancer. Genes not previously implicated in tumorigenesis were detected, as well as a set of 14 novel, highly conserved genes with here-to-fore unknown function. These studies define a set of transformation associated genes whose up-regulation has implications for understanding Src mediated transformation and strengthens the role of Src in the development and progression of human colon cancer. Supportive Supplemental Data can be viewed at http://pga.tigr.org/PGApubs.shtml.

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References

  • Akamatsu H, Ichihara-Tanaka K, Ozono K, Kamiike W, Matsuda H, Sekiguchi K . 1996 Cancer Res. 56: 4541–4546

  • Alter O, Brown PO, Botstein D . 2000 Proc. Natl. Acad. Sci. USA 97: 10101–10106

  • Ben-Dor A, Shamir R, Yakhini Z . 1999 J. Comput. Biol. 6: 281–297

  • Bjorge JD, Bellagamba C, Cheng HC, Tanaka A, Wang JH, Fujita DJ . 1995 J. Biol. Chem. 270: 2422–2428

  • Brown MT, Cooper JA . 1996 Biochim. Biophys. Acta 1287: 121–149

  • Byrne JA, Tomasetto C, Garnier JM, Rouyer M, Mattei MG, Bellocq JP, Rio MC, Basset P . 1995 Cancer Res. 55: 2896–2903

  • Chew CS, Parente JAJ, Chen X, Chaponnier C, Cameron RS . 2000 J. Cell Sci. 113: 2035–2045

  • DeRisi JL, Iyer VR, Brown PO . 1997 Science 278: 680–686

  • Eisen MB, Spellman PT, Brown PO, Botstein D . 1998 Proc. Natl. Acad. Sci. USA 95: 14863–14868

  • Freier S, Weiss P, Eran M, Flyvbjerg A, Dahan R, Nephesh I, Safra T, Shiloni E, Raz I . 1999 Gut 44: 704–708

  • Guo QM, Malek RL, Kim S, Chiao C, He M, Ruffy M, Sanka K, Lee NH, Dang CV, Liu ET . 2000 Cancer Res. 60: 5922–5928

  • Iba H, Takeya T, Cross FR, Hanafusa T, Hanafusa H . 1984 Proc. Natl. Acad. Sci. USA 81: 4424–4428

  • Inoue H, Pan J, Hakura A . 1998 J. Virol. 72: 2532–2537

  • Iravani S, Mao W, Fu L, Karl R, Yeatman T, Jove R, Coppola D . 1998 Lab. Invest. 78: 365–371

  • Irby RB, Mao W, Coppola D, Kang J, Loubeau JM, Trudeau W, Karl R, Fujita DJ, Jove R, Yeatman TJ . 1999 Nat. Genet. 21: 189–190

  • Johnson PJ, Coussens PM, Danko AV, Shalloway D . 1985 Mol. Cell. Biol. 5: 1073–1083

  • Jove R, Hanafusa H . 1987 Annu. Rev. Cell Biol. 3: 31–56

  • Jove R, Hanafusa T, Hamaguchi M, Hanafusa H . 1989 Oncogene Res. 5: 49–60

  • Kato JY, Takeya T, Grandori C, Iba H, Levy JB, Hanafusa H . 1986 Mol. Cell. Biol. 6: 4155–4160

  • Kraker AJ, Hartl BG, Amar AM, Barvian MR, Showalter HD, Moore CW . 2000 Biochem. Pharmacol. 60: 885–898

  • Kumble S, Omary MB, Cartwright CA, Triadafilopoulos G . 1997 Gastroenterology 112: 348–356

  • Lee NH, Malek RL . 1998 J. Biol. Chem. 273: 22317–22325

  • Lee Y, Sultana R, Pertea G, Cho J, Karamycheva S, Tsai J, Parvizi B, Cheug F, Antoescu V, White J, Holt I, Liang F, Quackenbush J . 2002 Genome Res. 12: 493–502

  • Levy JB, Iba H, Hanafusa H . 1986 Proc. Natl. Acad. Sci. USA 83: 4228–4232

  • Lutz MP, Esser IB, Flossmann-Kast BB, Vogelmann R, Luhrs H, Friess H, Buchler MW, Adler G . 1998 Biochem. Biophys. Res. Commun. 243: 503–508

  • Manenti S, Malecaze F, Chap H, Darbon JM . 1998 Cancer Res. 58: 1429–1434

  • Martin GS . 2001 Nat. Rev. Mol. Cell Biol. 2: 467–475

  • Miller LD, Park KS, Guo QM, Alkharouf NW, Malek RL, Lee NH, Liu ET, Cheng S . 2001 Mol. Cell. Biol. 21: 6626–6639

  • Muschel RJ, Williams JE, Lowy DR, Liotta LA . 1985 Am. J. Pathol. 121: 1–8

  • Niinaka Y, Paku S, Haga A, Watanabe J, Raz A . 1998 Cancer Res. 58: 2667–2674

  • Odajima J, Matsumura I, Sonoyama J, Daino H, Kawasaki A, Tanaka H, Inohara N, Kitamura T, Downward J, Nakajima K, Hirano T, Kanakura Y . 2000 J. Biol. Chem. 275: 24096–24105

  • Okamoto-Inoue M, Taniguchi S, Sadano H, Kawano T, Kimura G, Gabbiani G, Baba T . 1990 J. Cell Sci. 96: 631–637

  • Parker RC, Varmus HF, Bishop JM . 1984 Cell 37: 131–139

  • Quackenbush J, Liang F, Holt I, Petrea G, Upton J . 2000 Nucleic Acids Res. 28: 141–145

  • Raychaudhuri S, Stuart JM, Altman RB . 2000 Pac. Symp. Biocomput. 5: 455–466

  • Reimer CL, Borras AM, Kurdistani SK, Garreau JR, Chung M, Aaronson SA, Lee SW . 1999 J. Biol. Chem. 274: 11022–11029

  • Sabo SL, Ikin AF, Buxbaum JD, Greengard P . 2001 J. Cell Sci. 153: 1403–1414

  • Saitoh T, Sundsmo M, Roch JM, Kimura N, Cole G, Schubert D, Oltersdorf T, Schenk DB . 1989 Cell 58: 615–622

  • Schreiber V, Moog-Lutz C, Regnier CH, Chenard MP, Boeuf H, Vonesch JL, Tomasetto C, Rio MC . 1998 Mol. Med. 4: 675–687

  • Schubert D, Jin LW, Saitoh T, Cole G . 1989 Neuron 3: 689–694

  • Sefton BM, Hunter T, Beemon K, Eckhart W . 1980 Cell 20: 807–816

  • Shalloway D, Coussens PM, Yaciuk P . 1984 Proc. Natl. Acad. Sci. USA 81: 7071–7105

  • Skotzko M, Wu L, Anderson WF, Gordon EM, Hall FL . 1995 Cancer Res. 55: 5493–5498

  • Studler JM, Glowinski J, Levi-Strauss M . 1993 Eur. J. Neurosci 5: 614–623

  • Takekura N, Yasui W, Yoshida K, Tsujino T, Nakayama H, Kameda T, Yokozaki H, Nishimura Y, Ito H, Tahara E . 1990 Int. J. Cancer 45: 847–851

  • Takeya T, Hanafusa H . 1982 J. Virol. 44: 12–18

  • Talamonti MS, Roh MS, Curley SA, Gallick GE . 1993 J. Clin. Invest. 91: 53–60

  • Taylor SJ, Shalloway D . 1996 Bioessays 18: 9–11

  • Thomas SM, Brugge JS . 1997 Annu. Rev. Cell Dev. Biol. 13: 513–609

  • Wickus G, Gruenstein E, Robbins PW, Rich A . 1975 Proc. Natl. Acad. Sci. USA 72: 746–749

  • Yamashita A, Hakura A, Inoue H . 1999 Oncogene 18: 4777–4787

  • Yano M, Naito Z, Yokoyama M, Shiraki Y, Ishiwata T, Inokuchi M, Asano G . 1999 Cancer Lett. 22: 45–51

  • Yeung KY, Haynor DR, Ruzzo WL . 2001 Bioinformatics 17: 309–318

  • Zuber J, Tchernitsa OI, Hinzmann B, Schmitz AC, Grips M, Hellriegel M, Sers C, Rosenthal A, Schafer R . 2000 Nat. Genet. 24: 144–152

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Acknowledgements

We would like to thank Terry Utterback and the TIGR Sequencing Core Facility for their excellent sequencing support and Michael Heaney for database support. We would also like to acknowledge the exceptional efforts of the TIGR Gene Indices Group as well as the TMEV software developers. We would like to thank Dr Alan Kraker for Pfizer Global Research for generously providing PG180970. This study was supported in part by a National Heart Lung and Blood Institute Grant (HL59781, NH Lee), the National Cancer Institute (CA85052-01-A1 and CA85429-01, TJ Yeatman; CA77049-02 and 6120-119-L0-A, J Quackenbush), the American Cancer Society (ACSRPG99-099-01-MGO, TJ Yeatman).

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Authors and Affiliations

  1. Department of Functional Genomics, The Institute for Genomic Research, 9712 Medical Center Dr, Rockville, 20850, Maryland, MD, USA

    Renae L Malek, Kerry Lee, Sylvia Wong, Jennifer Tsai, Bryan Frank, John Quackenbush & Norman H Lee

  2. Department of Cancer and Cell Biology, Division of Clinical Science, Molecular Signaling and Oncogenesis Section, Medicine Branch, National Cancer Institute, Bethesda, 20892, Maryland, MD, USA

    Mei He & Edison T Liu

  3. Department of Surgery, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, College of Medicine, Tampa, 33612, Florida, FL, USA

    Rosalyn B Irby & Timothy J Yeatman

  4. Department of Oncology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, College of Medicine, Tampa, 33612, Florida, FL, USA

    Richard Jove

  5. Department of Biochemistry and Molecular Biology, H. Lee Moffitt Cancer Center & Research Institute, University of South Florida, College of Medicine, Tampa, 33612, Florida, FL, USA

    Richard Jove

  6. Cancer Biology Division, Johns Hopkins Cancer Center, Baltimore, 21231, Maryland, MD, USA

    Qingbin M Guo

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  1. Renae L Malek
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  2. Rosalyn B Irby
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  3. Qingbin M Guo
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  4. Kerry Lee
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Correspondence to Timothy J Yeatman or Norman H Lee.

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Malek, R., Irby, R., Guo, Q. et al. Identification of Src transformation fingerprint in human colon cancer. Oncogene 21, 7256–7265 (2002). https://doi.org/10.1038/sj.onc.1205900

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