Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

Identification of genes involved in epithelial-mesenchymal transition and tumor progression

Oncogene volume 20, pages 6679–6688 (2001)Cite this article

Abstract

The adenovirus E1A12S gene product (WT12S) immortalizes epithelial cells and they retain their differentiated characteristics, but certain mutants cannot do the latter. Characterization of mutant immortalized epithelial cells indicated that they had undergone epithelial mesenchymal transition (EMT). Coexpression of V12ras with WT12S leads to benign tumors, but to malignant tumors with 12S mutants. Since EMT is critical for tumor progression, identification of the molecular mechanisms involved should elucidate novel therapeutic targets. To this end, representational difference analysis (RDA) was used to identify cDNAs upregulated in the mutant cell line. Thirty-five differentially expressed mRNAs were identified and classified into several functional categories, including nine novel cDNAs. Among the 26 known cDNAs, extracellular matrix and related proteins made up the largest group of differentially expressed genes, followed by growth factors and receptors and transcription factors. There was also an ion transporter, a cytoskeletal protein, glycosylation and amidinotransferase enzymes and proteins with unknown functions. Some of the known genes have previously been associated with EMT and/or tumor progression and thus served to validate the system to obtain the desired target genes, while other cDNAs are newly linked with dedifferentiation/malignancy. Array analyses indicated that the cDNAs were specifically upregulated in invasive or metastatic tumors, especially of breast, uterus and lung, suggesting their involvement in the progression of these tumors.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  • Adachi E, Hopkinson I, Hayashi T . 1997 Int. Rev. Cytol. 173: 73–156

  • Allgayer H, Babic R, Grutzner KU, Beyer BC, Tarabichi A, Schildberg FW, Heiss MM . 1998 Clin. Exp. Metastasis 16: 62–73

  • Ben-Baruch N, Yarden Y . 1994 Proc. Soc. Exp. Biol. Med. 206: 221–227

  • Birchmeier W, Behrens J, Weidner KM, Hulsken J, Birchmeier C . 1996 Curr. Top. Microbiol. Immunol. 213: 117–135

  • Boyer B, Valles AM, Edme N . 2000 Biochem. Pharmacol. 60: 1091–1099

  • Brenner W, Gross S, Steinbach F, Horn S, Hohenfellner R, Thuroff JW . 2000 Cancer Lett. 155: 199–205

  • Chinnadurai G . 1992 Oncogene 7: 1255–1258

  • Crossin KL, Krushel LA . 2000 Dev. Dyn. 218: 260–279

  • Daniel L, Trouillas J, Renaud W, Chevallier P, Gouvernet J, Rougon G, Figarella-Branger D . 2000 Cancer Res. 60: 80–85

  • Dennis JW, Granovsky M, Warren CE . 1999 Biochim. Biophys. Acta. 1473: 21–34

  • Dobra K, Andang M, Syrokou A, Karamanos NK, Hjerpe A . 2000 Exp. Cell Res. 258: 12–22

  • Douglas JL, Gopalakrishnan S, Quinlan MP . 1991 Oncogene 6: 2093–2103

  • Duncan EL, Reddel RR . 1997 Biochemistry 62: 1263–1274

  • Eccles MR . 1998 Pediatr. Nephrol. 12: 712–720

  • Fearon ER, Vogelstein B . 1990 Cell 61: 759–767

  • Feige JJ, Negoescu A, Keramidas M, Souchelnitskiy S, Chambaz EM . 1996 Horm. Res. 45: 227–232

  • Fimia GM, De Cesare D, Sassone-Corsi P . 2000 Mol. Cell. Biol. 20: 8613–8622

  • Fischer RS, Quinlan MP . 1998a Virology 249: 427–439

  • Fischer RS, Quinlan MP . 1998b Cell Growth Differ. 9: 905–918

  • Fischer RS, Quinlan MP . 2000 Virology 269: 404–419

  • Friedlander A, Patarca R . 1999 Crit. Rev. Oncog. 10: 161–238

  • Fujiwara Y, Ohata H, Kuroki T, Koyama K, Tsuchiya E, Monden M, Nakamura Y . 1995 Oncogene 10: 891–895

  • Grimm S, Weinstein EJ, Krane IM, Leder P . 1998 J. Exp. Med. 188: 1535–1539

  • Guthmiller P, Van Pilsum JF, Boen JR, McGuire DM . 1994 J. Biol. Chem. 269: 17556–17560

  • Haralson MA, DiMari SJ, Hoover RL, Harris RC . 2000 Matrix Biol. 19: 47–59

  • Hargrave M, Wright E, Kun J, Emery J, Cooper L, Koopman P . 1997 Dev. Dyn. 210: 79–86

  • Hay ED . 1995 Acta Anat. 154: 8–20

  • He Z, Bateman A . 1999 Cancer Res. 59: 3222–3229

  • Hecht G, Koutsouris A . 1999 Am. J. Physiol. 277: C441–C447

  • Houweling A, van den Elsen PJ, van der Eb AJ . 1980 Virology 105: 537–550

  • Hubank M, Schatz DG . 1994 Nucleic Acids Res. 22: 5640–5648

  • Huber SM, Braun GS, Segerer S, Veh RW, Horster MF . 2000 Am. J. Physiol. Renal Physiol. 279: F65–F76

  • Humm A, Huber R, Mann K . 1994 FEBS Lett. 339: 101–107

  • Isaac L, Florido MP, Fecchio D, Singer LM . 1999 Inflamm. Res. 48: 446–452

  • Kanwar YS, Ota K, Yang Q, Kumar A, Wad J, Kashihara N, Peterson DR . 1998 Am. J. Physiol. 275: F710–F723

  • Kirschmann DA, Seftor EA, Nieva DR, Mariano EA, Hendrix MJ . 1999 Breast Cancer Res. Treat. 55: 127–136

  • Komiya A, Suzuki H, Ueda T, Aida S, Ito N, Shiraishi T, Yatani R, Emi M, Yasuda K, Shimazaki J, Ito H . 1997 Jpn. J. Cancer Res. 88: 389–393

  • Kuppuswamy M, Subramanian T, Chinnadurai G . 1988 Oncogene 2: 613–615

  • Lee SM, Tsui SK, Chan KK, Garcia-Barcelo M, Waye MM, Fung P, Liew CC, Lee CY . 1998 Gene 216: 163–170

  • Linder S, Popowicz P, Svensson C, Marshall H, Bondesson M, Akusjarvi G . 1992 Oncogene 7: 439–443

  • Lipschutz JH . 1998 Am. J. Kidney Dis. 31: 383–397

  • Lohi J, Leivo I, Oivula J, Lehto VP, Virtanen I . 1998 Histol. Histopathol. 13: 785–796

  • Lombardi D, Lacombe Ml, Paggi MG . 2000 J. Cell. Physiol. 182: 144–149

  • Looijenga LH, Gillis AJ, van Gurp RJ, Verkerk AJ, Oosterhuis JW . 1997 Am. J. Pathol. 151: 581–590

  • Lyon MF . 1999 Curr. Biol. 9: R235–R237

  • McDonald HL, Gascoyne RD, Horsman D, Brown CJ . 2000 Genes Chromosomes Cancer 28: 246–257

  • Miner JH . 1999 Kidney Int. 56: 2016–2024

  • Mitchell MS, Kan-Mitchel J, Minev B, Edman C, Deans RJ . 2000 Cancer Res. 60: 6448–6456

  • Montano X, Lane DP . 1987 Mol. Cell Biol. 7: 1782–1790

  • Mrowka C, Schedl A . 2000 J. Am. Soc. Nephrol. 11 Suppl 16 S106–S115

  • Muller W, Schneiders A, Hommel G, Gabbert HE . 1998 Cancer 83: 2481–2487

  • Mymryk JS . 1996 Oncogene 13: 1581–1589

  • Oivula J, Lohi J, Tani T, Kangas L, Kiviluoto T, Kivilaakso E, Butkowski R, Virtanen I . 1999 J. Pathol. 187: 455–461

  • Okabe-Kado J, Kasukabe T, Honma Y . 1998 Leuk. Lymphoma 32: 19–28

  • Okada H, Danoff TM, Kalluri R, Neilson EG . 1997 Am. J. Physiol. 273: F563–F574

  • Panet R, Marcus M, Atlan H . 2000 J. Cell. Physiol. 182: 109–118

  • Peyrard M, Seroussi E, Sandberg-Nordqvist AC, Xie YG, Han FY, Fransson I, Collins J, Dunham I, Kost-Alimova M, Imreh S, Dumanski JP . 1999 Proc. Natl. Acad. Sci. USA 96: 598–603

  • Plisov SY, Ivanov SV, Yoshino K, Dove LF, Plisova TM, Higinbotham KG, Karavanova I, Lerman M, Perantoni AO . 2000 Genesis 27: 22–31

  • Pujuguet P, Simian M, Liaw J, Timpl R, Werb Z, Bissell MJ . 2000 J. Cell. Sci. 113: 849–858

  • Quinlan MP . 1989 Oncogene 4: 1051–1055

  • Quinlan MP . 1993 Oncogene 8: 3289–3296

  • Quinlan MP, Douglas JL . 1992 J. Virol. 66: 2020–2030

  • Quinlan MP, Grodzicker T . 1987 J. Virol. 61: 673–682

  • Quinlan MP, Whyte P, Grodzicker T . 1988 Mol. Cell Biol. 8: 3191–3203

  • Ramirez F, Pereira L . 1999 Int. J. Biochem. Cell Biol. 31: 255–259

  • Reddel RR . 2000 Carcinogenesis 21: 477–484

  • Saito H, Papaconstantinou J, Sato H, Goldstein S . 1997 J. Biol. Chem. 272: 8157–8160

  • Schneider J, Pollan M, Jimenez E, Marenbach K, Martinez N, Volm M, Marx D, Meden H . 2000 Br. J. Cancer 82: 1662–1670

  • Smith-Mungo LI, Kagan HM . 1998 Matrix Biol. 16: 387–398

  • Sterzel RB, Hartner A, Schlotzer-Schrehardt U, Voit S, Hausknecht B, Doliana R, Colombatti A, Gibson MA, Braghetta P, Bressan GM . 2000 Kidney Int. 58: 1588–1602

  • Stohr H, Marquardt A, White K, Weber BH . 2000 Cytogenet. Cell Genet. 88: 211–216

  • Stokes MB, Holler S, Cui Y, Hudkins KL, Eitner F, Fogo A, Alpers CE . 2000 Kidney Int. 57: 487–498

  • Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE, Neilson EG . 1995 J. Cell. Biol. 130: 393–405

  • Subramanian T, La Regina M, Chinnadurai G . 1989 Oncogene 4: 415–420

  • van Goor H, Diamond JR, Ding G, Kaysen G . 1999 Exp. Nephrol. 7: 35–43

  • Wada J, Kumar A, Ota K, Wallner EI, Batlle DC, Kanwar YS . 1997 Kidney Int. 51: 1629–1638

  • Weiler SR, Taylor SM, Deans RJ, Kan-Mitchell J, Mitchell MS, Trent JM . 1994 Genomics 22: 243–244

  • Wilda M, Bachner D, Just W, Geerkens C, Kraus P, Vogel W, Hameister H . 2000 J. Bone. Miner. Res. 15: 2187–2196

  • Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M . 2000 J. Biol. Chem. 275: 33669–33678

  • Yang Q, Ota K, Tian Y, Kumar A, Wada J, Kashihara N, Wallner E, Kanwar YS . 1999 Dev. Biol. 212: 229–242

  • Zhang H, Serrero G . 1998 Proc. Natl. Acad. Sci. USA 95: 14202–14207

Download references

Acknowledgements

The authors appreciate the support of K Sakurada, the advice and assistance of H Yoshisue and critical reading of the manuscript by S Sharma. AK Kiemer was supported by the ‘Bayerischer Habilitationsförderpreis’ and by the ‘Kollegium für ärztliche Fortbildung e.V.’, Regensburg, Germany/the ASTA Medica AG, Frankfurt, Germany.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Center of Drug Research, University of Munich, Butenandtstr. 5-13, Munich, 81377, Germany

    Alexandra K Kiemer

  2. Kyowa Hakko Kogyo, Tokyo Research Laboratories, 3-6-6 Asahi-machi, Machida-shi, 194-8533, Tokyo, Japan

    Kyoko Takeuchi & Margaret P Quinlan

Authors
  1. Alexandra K Kiemer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyoko Takeuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Margaret P Quinlan
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Margaret P Quinlan.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kiemer, A., Takeuchi, K. & Quinlan, M. Identification of genes involved in epithelial-mesenchymal transition and tumor progression. Oncogene 20, 6679–6688 (2001). https://doi.org/10.1038/sj.onc.1204872

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1204872

Keywords

This article is cited by

Search

Advanced search

Quick links