Skip to main content

Advertisement

Log in

Analysis of DLC-1 expression in human breast cancer

  • Original Paper
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

The chromosome region 8p12-p22 shows frequent allelic loss in many neoplasms, including breast cancer (BC). The DLC-1 gene, located on 8p21-p22, might be a candidate tumor suppressor gene in this region. To evaluate the involvement of DLC-1 in breast carcinogenesis we studied DLC-1 mRNA expression in a panel of 14 primary human BC and the corresponding normal breast cells as well as 8 BC cell lines. Low levels or absence of DLC-1 mRNA were observed in 57% of primary BC and 62.5% of BC cell lines, respectively. We could not find any correlation between DLC-1mRNA expression and deletions at the DLC-1 locus. Transfection of the gene into DLC-1 deficient T-47D cells raised the DLC-1 mRNA level and resulted in inhibition of cell growth and reduced colony-forming capacity. Our results indicate a role of DLC-1 in BC carcinogenesis.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1.
Fig. 2.
Fig. 3.

Similar content being viewed by others

References

  • Adélaide J, Chaffanet M, Imbert A, Allione F, Geneix J, Popovici C, van Alewijk D, Trapman J, Zeillinger R, Borresen-Dale AL, Lidereau R, Birnbaum D, Pebusque MJ (1998) Chromosome region 8p11-p21: refined mapping and molecular alterations in breast cancer. Genes Chromosomes Cancer 22:186–199

    Article  PubMed  Google Scholar 

  • Ambashagan R, Fujii H, Gabrielson E (1998) Allelic loss of chromosomal arm 8p in breast cancer progression. Am J Pathol 152:815–819

    PubMed  Google Scholar 

  • Choi C, Kim MH, Juhng SW, Oh BR (2000) Loss of heterozygosity at chromosome segments 8p22 and 8p11.2–21.1 in transitional-cell carcinoma of the urinary bladder. Int J Cancer 86:501–505

    Article  CAS  PubMed  Google Scholar 

  • El-Naggar AK, Coombes MM, Batsakis JG, Hong WK, Goepfert H, Kagan J (1998) Localization of chromosome 8p regions in valued in early tumorigenesis of oral and laryngeal squamous carcinoma. Onocgene 16:2983–2987

    Article  CAS  Google Scholar 

  • Farrington SM, Cunningham C, Boyle SM, Wyllie Ah, Dunlop MG (1996) Detailed physical and deletion mapping of 8p with isolation of YAC clones from tumour suppressor loci involved in colorectal cancer. Oncogene 12:1803–1808

    CAS  PubMed  Google Scholar 

  • Goldberg EK, Glendening M, Karanjawala Z, Sridhar A, Walker GJ, Hayward NK, Rice AJ, Kurera D, Tebha Y, Fountain JW (2000) Localization of multiple melanoma tumor-suppressor genes on chromosome 11 by use of homozygosity mapping-of-deletion analysis. Am J Hum Genet 67:417–431

    Article  CAS  PubMed  Google Scholar 

  • Hamaguchi M, Meth JL, von Clitzing C, Wei W, Esposito D, Rodgers L, Walsh T, Welcsh P, King M-C, Wigle MH (2002) DBC2, a candidate for a tumor suppressor gene involved in breast cancer. Proc Natl Acad Sci USA 99:1347–13652

    Article  PubMed  Google Scholar 

  • Ishii H, Vecchione A, Murakumo Y, Baldassarre G, Numata S, Trapasso F, Alder H, Baffa R, Croce CM (2001) FEZ1/LZTS1 gene at 8p22 suppresses cancer cell growth and regulates mitosis. Proc Natl Acad Sci USA 98:10374–10379

    Article  CAS  PubMed  Google Scholar 

  • Kerangueven F, Essioux L, Dib A, Noguchi T, Allione F, Geneix J, Longy M, Lidereau R, Eisinger F, Pebusque MJ, Jacquemier J, Bonaiti-Pellie C, Sobol H, Birnbaum D (1995) Loss of heterozygosity and linkage analysis in breast carcinoma: indication for a putative third susceptibility gene on the short arm of chromosome 8. Oncogene 10:1023–1026

    CAS  PubMed  Google Scholar 

  • Ng IO, Liang ZD, Cao L, Lee TK (2000) DLC-1 is deleted in primary hepatocellular carcinoma and exerts inhibitory effects on the proliferation of hepatoma cell lines with deleted DLC-1. Cancer Res 60:6581–6584

    CAS  PubMed  Google Scholar 

  • Peck J, Douglasiv G, Wu CH, Burbelo PD (2000) Human RhoGAP domain-containing proteins: Structure, function and evolutionary relationship. FEBS Lett 528:27–34

    Article  Google Scholar 

  • Pineau P, Nagai H, Prigent S, Wei Y, Gyapay G, Weissenbach J, Tiollais P, Buendia MA, Dejean A (1999) I dentification of three distinct regions of allelic deletions on the short arm of chromosome 8 in hepatocellular carcinoma. Oncogene 18:3127–3134

    CAS  PubMed  Google Scholar 

  • Pribill I, Speiser P, Leary J, Leodolter S, Hacker NF, Friedlander ML, Birnbaum D, Zeillinger R, Krainer M (2001) High frequency of allelic imbalance at regions of chromosome arm 8p in ovarian carcinoma. Cytogenet Cell Genet 129:23–29

    Article  CAS  Google Scholar 

  • Sato K, Qian J, Slezak JM, Lieber MM, Bostwick DG, Bergstralh EJ, Jenkins RB (1999) Clinical significance of alterations of chromosome 8 in high-grade, advanced, nonmetastatic prostate carcinoma. J Nat Cancer Inst 91:1574–1580

    Article  CAS  Google Scholar 

  • Schmitz AAP, Govek EE, Böttner B, van Aelst L (2000) Rho GTPases: Signaling, migration, and invasion. Exp Cell Res 261:1–12

    CAS  PubMed  Google Scholar 

  • Seitz S, Rohde K, Bender E, Nothnagel A, Pidde H, Ullrich OM, El-Zeheiry A, Haensch W, Jandrig B, Kölble K, Schlag PM, Scherneck S (1997a) Deletion mapping and linkage analysis provide strong indication for the involvement of the human chromosome region 8p12-p22 in breast carcinogenesis. Br J Cancer 76:983–991

    CAS  PubMed  Google Scholar 

  • Seitz S, Rohde K, Bender E, Nothnagel A, Kölble K, Schlag PM, Scherneck S (1997b) Strong indication for a breast cancer susceptibility gene on chromosome 8p12-p22: linkage analysis in German breast cancer families. Oncogene 14:741–743

    Google Scholar 

  • Seitz S, Werner S, Fischer J, Nothnagel A, Schlag PM, Scherneck S (2000) Refined deletion mapping in sporadic breast cancer at chromosomal region 8p12-p21 and association with clinicopathological parameters. Eur J Cancer 36:1507–1513

    Article  CAS  PubMed  Google Scholar 

  • Seitz S, Wassmuth P, Fischer J, Nothnagel A, Jandrig B, Schlag PM, Scherneck S (2002) Mutation analysis and mRNA expression of TRAIL-receptors in human breast cancer. Int J Cancer 102:117–128

    Article  CAS  PubMed  Google Scholar 

  • Ugolini F, Adélaide J, Charafe-Jauffret E, Nguyen C, Jacquemir J, Jordan B, Birnbaum D, Pebusque M-J (1999) Differential expression assay of chromosome arm 8p genes identifies frizzle-related (FRP1/FRZB) and fibroblast growth factor receptor 1 (FGFR1) as candidate breast cancer genes. Oncogene 18:1903–1910

    Article  CAS  PubMed  Google Scholar 

  • Washburn JG, Wojno KJ, Dey J, Powell IJ, Macoska JA (2000) 8pter-p23 deletion is associated with racial differences in prostate cancer outcome. Clin Cancer Res 6:4647–4652

    CAS  PubMed  Google Scholar 

  • Wilson PJ, McGlinn E, Marsh A, Evans T, Arnold J, Wright K, Biden K, Young J, Weinwright B, Wicking C, Chenevix-Tranch, G (2000) Sequence variants of DLC-1 in colorectal and ovarian tumours. Hum Mutat 15:156–165

    Article  CAS  PubMed  Google Scholar 

  • Wistuba II, Behrens C, Virmani AK, Milchgrub S, Syed S, Lam S, Mackay B, Minna JD, Gazdar AF (1999) Allelic losses at chromosome 8p21–23 are early and frequent events in the pathogenesis of lung cancer. Cancer Res 59:1973–1979

    CAS  PubMed  Google Scholar 

  • Yin XL, Pang JC, Ng HK (2000) Identification of a region of homozygous deletion on 8p22–23.1 in medulloblastoma. Oncogene 21:1461–1468

    Article  Google Scholar 

  • Yokota T. Yoshimoto M, Akiyama F, Sakameto G, Kasumi F, Nakamura Y, Emi M (1999) Localization of a tumor suppressor gene associated with the progression of human breast carcinoma within a 1-cM interval of 8p22-p23.1. Cancer 85:447–452

    Article  CAS  PubMed  Google Scholar 

  • Yuan B-Z, Miller MJ, Keck CL, Zimonjic DB, Thorgeirsson SS, Popescu NC (1998) Cloning, characterization and chromosomal localization of a gene frequently deleted in human liver Cancer (DLC-1) homologous to rat RhoGAP. Cancer Res 58:2196–2199

    CAS  PubMed  Google Scholar 

  • Yuan B-Z, Thorgeirsson SS, Eyfjord J, Gudmundsdottir K, Popescu NC (2000) Genomic deletion and DNA hypermethylation of DLC-1, a candidate tumor suppressor gene in several human solid tumors. Proc Am Assoc Cancer Res 41:105

    Google Scholar 

Download references

Acknowledgements

We thank Sabine Werner for excellent technical assistance. This work was supported by the Deutsche Krebshilfe grant 70–2701.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Marlies Plaumann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Plaumann, M., Seitz, S., Frege, R. et al. Analysis of DLC-1 expression in human breast cancer. J Cancer Res Clin Oncol 129, 349–354 (2003). https://doi.org/10.1007/s00432-003-0440-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00432-003-0440-z

Keywords

Navigation