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:

A network of clinically and functionally relevant genes is involved in the reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after transfer of human chromosome 8

Oncogene volume 24, pages 869–879 (2005)Cite this article

Abstract

Several investigations have supposed that tumor suppressor genes might be located on human chromosome 8. We used microcell-mediated transfer of chromosome 8 into MDA-MB-231 breast cancer cells and generated independent hybrids with strongly reduced tumorigenic potential. Loss of the transferred chromosome results in reappearance of the malignant phenotype. Expression analysis identified a set of 109 genes (CT8-ps) differentially expressed in microcell hybrids as compared to the tumorigenic MDA-MB-231 and rerevertant cells. Of these, 44.9% are differentially expressed in human breast tumors. The expression pattern of CT8-ps was associated with prognostic factors such as tumor size and grading as well as loss of heterozygosity at the short arm of chromosome 8. We identified CT8-ps networks suggesting that these genes act cooperatively to cause reversion of tumorigenicity in MDA-MB-231 cells. Our findings provide a conceptual basis and experimental system to identify and evaluate genes and gene networks involved in the development and/or progression of breast cancer.

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

  • Arnold N, Hägele L, Walz L, Schempp W, Pfisterer J, Bauknecht T and Kiechle M . (1996). Genes Chromosomes Cancer, 16, 46–54.

  • Behrens P, Jeske W, Wernet N and Wellmann A . (2001). Pathobiology, 69, 19–23.

  • Borg A, Ferno M and Peterson C . (2003). Nat. Med., 9, 16–18.

  • Goldberg EK, Glendening M, Karanjawala Z, Shridhar A, Walker GS, Hayward NK, Rice AJ, Kurera D, Tebha Y and Fountain JW . (2000). Am. J. Hum. Genet., 67, 417–431.

  • Gudas JM, Payton M, Thukral S, Chen E, Bass M, Robinson MO and Coats S . (1999). Mol. Cell. Biol., 19, 12–22.

  • Gustafson CE, Wilson PJ, Lukeis R, Baker E, Woollatt E, Annab L, Hawke L, Barrett JC and Chenevix-Trench G . (1996). Cancer Res., 56, 5238–5245.

  • Hogue DA, Clines G, Lovett M, Hansen MF and Hecht JT . (1996). Am. J. Hum. Genet., 56, A15–A21.

  • Huang E, Cheng SH, Dressman H, Pittman J, Tsou MH, Horng CF, Bild A, Iversen ES, Liao M, Chen CM, West M, Nevins JR and Huang AT . (2003). Lancet, 10, 1590–1596.

  • Jenssen TK, Laegreid A, Komorowski J and Hovig E . (2001). Nat. Genet., 28, 21–28.

  • Jones SE and Jomary C . (2002). Int. J. Biochem. Cell Biol., 34, 427–431.

  • Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA and Massague J . (2003). Cancer Cell, 3, 537–549.

  • Khatri P, Draghici S, Ostermeier GC and Krawetz SA . (2002). Genomics, 79, 266–270.

  • Kim B-T, Kitagawa H, Tamura J-I, Saito T, Kusche-Gullberg M, Lindahl U and Sugahara K . (2001). Proc. Natl. Acad. Sci. USA, 98, 7176–7181.

  • Kugoh H, Nakamoto H, Inoue J, Funaki K, Barrett JC and Oshimura M . (2002). Mol. Carcinogen., 35, 148–156.

  • Lerebours F and Lidereau R . (2002). Crit. Rev. Oncol. Hemat., 44, 121–141.

  • Logan GJ, Smyth CM, Earl JW, Zaikina I, Rowe PB, Smythe JA and Alexander IE . (2002). Immunology, 28, 105478–105487.

  • Murakami Y . (2002). Oncogene, 21, 6936–6948.

  • Nihei N, Kouprina N, Larionov V, Oshima J, Martin GM, Ichikawa T and Barrett JC . (2002). Cancer Res., 62, 367–370.

  • Payton M, Scully S, Chung G and Coats S . (2002). Oncogene, 21, 8529–8534.

  • Primakoff D and Myles DG . (2000). Trends Genet., 16, 83–87.

  • Pucci S, Bonanno E, Pichiorri F, Angeloni C and Spagnoli LG . (2004). Oncogene, 23, 2298–2304.

  • Redondo M, Villar E, Torres-Munoz J, Tellez T, Morell M and Petito CK . (2000). Am. J. Pathol., 157, 393–399.

  • Rennstam K, Ahlstedt-Soini M, Baldetorp B, Bendahl PO, Borg A, Karhu R, Tanner M, Tirkkonen M and Isola J . (2003). Cancer Res., 63, 8861–8868.

  • Saffer H, Wahed A, Rassidakis GZ and Medeiros LJ . (2002). Mod. Pathol., 15, 1221–1226.

  • Sambrook J, Fritsch EF and Maniatis T . (1989). Molecular Cloning: A Laboratory Manual. Cold Spring Harbor Laboratory Press: New York.

    Google Scholar 

  • Scaltriti M, Brausi M, Amorosi A, Caporali A, D'Arca D, Astancolle S, Corti A and Bettuzzi S . (2004). Int. J. Cancer., 108, 23–30.

  • Schlitt T, Palin K, Runa J, Dietmann S, Lappe M, Ukkonen E and Brazma A . (2003). Genome Res., 13, 2568–2576.

  • Seitz S, Rohde K, Bender E, Nothnagel A, Pidde H, Ulrich O-M, El-Zehairy A, Haensch W, Jandrig B, Koelble K, Schlag PM and Scherneck S . (1997). Br. J. Cancer, 76, 983–991.

  • Seitz S, Wassmuth P, Plaschke J, Schackert HK, Karsten U, Santibanez-Koref MF, Schlag PM and Scherneck S . (2003). Genes Chromosomes Cancer, 37, 29–35.

  • Seitz S, Werner S, Fischer J, Nothnagel A, Schlag PM and Scherneck S . (2000). Eur. J. Cancer, 36, 1507–1513.

  • Singh B, Ittmann MM and Krolewski JJ . (1998). Genes Chromosomes Cancer, 21, 166–171.

  • Steinberg J, Oyasu R, Lang S, Sintich S, Rademaker A, Lee C, Kozlowski JM and Lee C . (1997). Clin. Cancer Res., 3, 1807–1811.

  • Strezoska Z, Pestov DG and Lau LF . (2002). J. Biol. Chem., 277, 29617–29625.

  • Suzuki A, Shao X, Song X-Q, Hanaoka T, Lrie S, Kashinwada M, Samara G, Close LG, Aoki T, Fujimori M, Ishikawa Y, Hatori M, Hosaka M, Sakurada A, Sato M, Ohuchi N, Satomi S, Fukushige S, Horii A and Sato T . (1999). Int. J. Oncol., 15, 443–451.

  • Theile M, Hartmann S, Naundorf H, Rueß D, Elbe B, Krause H, Deppert W, Barrett JC and Scherneck S . (1994). Int. J. Oncol., 4, 1067–1075.

  • Trougakos IP and Gonos ES . (2002). Int. J. Biochem. Cell Biol., 34, 1430–1448.

  • Tsuneizumi M, Emi M, Hirano A, Utada Y, Tsumagari K, Takahashi K, Kasumi F, Akiyama F, Sakomoto G, Kazui T and Nakamura Y . (2002). Cancer Lett., 180, 75–82.

  • van't Veer LJ, Dai H, van de Vijver MJ, He YD, Hart AA, Mao M, Peterse HL, van der Kooy K, Marton MJ, Witteveen AT, Schreiber GJ, Kerkhoven RM, Roberts C, Linsley PS, Bernards R and Friend SH . (2002). Nature, 415, 530–536.

  • Weimer J, Kiechle M and Arnold N . (2000). Cytogenet. Cell Genet., 88, 114–118.

  • Weimer J, Kiechle M, Senger G, Wiedemann U, Ovens-Raeder A, Schuierer S, Kautza M, Siebert R and Arnold N . (1999). Chromosome Res., 7, 355–362.

  • Wilson P, Cuthbert A, Marsh A, Arnold J, Flanagan J, Malford C, Trott D, Baker E, Purdie D, Newbold R and Chenevix-Trench G . (2003). Cancer Genet. Cytogenet., 143, 100–112.

  • Yaremko ML, Kutza C, Lyzak J, Mick R, Recan WM and Westbrook CA . (1996). Genes Chromosomes Cancer, 16, 189–195.

  • Zhang RD, Fidler IJ and Price JE . (1991). Invas. Metast., 11, 204–215.

Download references

Acknowledgements

We thank M-F Santibanez-Koref for helpful comments on this manuscript. We are indebted to K Poppe, S Werner, J Strissel, P Waßmuth for technical assistance and J Fischer for performing statistical analyses. This work was partially supported by the Deutsche Krebshilfe Grant 70-2701.

Author information

Authors and Affiliations

  1. Department of Tumor Genetics, Max Delbrueck Center for Molecular Medicine, Robert Roessle Str. 10, 13125, Berlin, Germany

    Susanne Seitz, Renate Frege & Siegfried Scherneck

  2. Oncology Laboratory, Gynecology and Obstetrics Clinic, University Hospital Schleswig-Holstein Campus Kiel, Michalisstr. 16, 24105, Kiel, Germany

    Anja Jacobsen, Jörg Weimer & Norbert Arnold

  3. atugen AG, Wiltbergstr. 50, 13125, Berlin, Germany

    Wolfgang Arnold

  4. Department of Hematology, Oncology and Tumor Immunology, Charite-Campus Berlin-Buch, Humboldt University, Lindenberger Weg 80, 13125, Berlin-Buch, Germany

    Clarissa von Haefen

  5. Department of Gynecology and Obstetrics, University of Duesseldorf, Moorenstr. 5, 40225, Duesseldorf, Germany

    Dieter Niederacher

  6. Department of Molecular Gynecology and Oncology, Gynecology and Obstetrics Clinic, Kerpener Str. 34, 50931, Köln, Germany

    Rita Schmutzler

Authors
  1. Susanne Seitz
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Renate Frege
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Anja Jacobsen
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jörg Weimer
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wolfgang Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Clarissa von Haefen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Dieter Niederacher
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Rita Schmutzler
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Norbert Arnold
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Siegfried Scherneck
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Susanne Seitz.

Additional information

Supplementary information accompanies the paper on Oncogene website (http://www.nature.com/onc).

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Seitz, S., Frege, R., Jacobsen, A. et al. A network of clinically and functionally relevant genes is involved in the reversion of the tumorigenic phenotype of MDA-MB-231 breast cancer cells after transfer of human chromosome 8. Oncogene 24, 869–879 (2005). https://doi.org/10.1038/sj.onc.1208260

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1208260

Keywords

Search

Advanced search

Quick links