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Breast Cancer Research and Treatment

, Volume 103, Issue 3, pp 283–291 | Cite as

Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer

  • Gerwin Heller
  • Joseph Geradts
  • Barbara Ziegler
  • Irene Newsham
  • Martin Filipits
  • Eva-Maria Markis-Ritzinger
  • Daniela Kandioler
  • Walter Berger
  • Wolfgang Stiglbauer
  • Dieter Depisch
  • Robert Pirker
  • Christoph C. Zielinski
  • Sabine Zöchbauer-Müller
Preclinical Study

Abstract

TSLC1 and DAL-1 are tumor suppressor genes involved in cell adhesion. In this study, we examined the expression and methylation pattern of these genes in breast cancer cell lines and primary breast carcinomas. TSLC1 expression was lost in 5 of 8 (63%) and DAL-1 expression was lost in 6 of 8 (75%) breast cancer cell lines, respectively. Downregulation of TSLC1 expression was observed in 43 of 50 (86%) and of DAL-1 expression in 26 of 55 (47%) primary breast carcinomas. TSLC1 methylation was found in 4 of 8 (50%) and DAL-1 methylation was observed in 6 of 8 (75%) breast cancer cell lines, respectively. Of 95 primary breast carcinomas 46 (48%) were TSLC1 methylated and 26 (27%) were DAL-1 methylated. Twenty of 43 (47%) and 10 of 26 (38%) primary breast cancer samples which showed downregulation of TSLC1 and DAL-1 expression were unmethylated for these genes. Re-expression of TSLC1 and DAL-1 was observed after treatment of BT-20 cells with 5-aza-2′-deoxycytidine and TSA. Samples from patients with grade 3 tumors were more frequently TSLC1 and TSLC1 and/or DAL-1 methylated than samples from patients with grade 1 and 2 tumors (P = 0.032, P = 0.023). Moreover, TSLC1 methylation correlated with loss of both ER and PgR staining (P = 0.011, P = 0.02). Our findings suggest that TSLC1 and DAL-1 are involved in the pathogenesis of breast cancer and are frequently inactivated by methylation.

Keywords

Tumor suppressor gene TSLC1 DAL-1 Methylation Breast cancer 

Notes

Acknowledgments

This study was supported by grants from the Austrian Federal Ministry of Education, Science and Culture (GZ 200.062/2-VI/1/2002), by the Medical-Scientific Fund of the Mayor of the Federal Capital Vienna, by an award from the “Fonds der Stadt Wien für Innovative Interdisziplinäre Krebsforschung” and by the Ludwig Boltzmann Institute for Clinical and Experimental Oncology.

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Copyright information

© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  • Gerwin Heller
    • 1
    • 2
  • Joseph Geradts
    • 3
  • Barbara Ziegler
    • 1
    • 2
  • Irene Newsham
    • 4
  • Martin Filipits
    • 5
  • Eva-Maria Markis-Ritzinger
    • 6
  • Daniela Kandioler
    • 7
  • Walter Berger
    • 5
  • Wolfgang Stiglbauer
    • 6
  • Dieter Depisch
    • 8
  • Robert Pirker
    • 1
    • 2
  • Christoph C. Zielinski
    • 1
    • 2
  • Sabine Zöchbauer-Müller
    • 1
    • 2
  1. 1.Clinical Division of Oncology, Department of Medicine IMedical University of ViennaViennaAustria
  2. 2.Center of Excellence in Clinical and Experimental OncologyMedical University of ViennaViennaAustria
  3. 3.Department of PathologyDuke University Medical CenterDurhamUSA
  4. 4.Brain Tumor Center, Department of Neuro-OncologyM. D. Anderson Cancer CenterHoustonUSA
  5. 5.Institute of Cancer ResearchMedical University of ViennaViennaAustria
  6. 6.Department of PathologyGeneral Hospital Wiener NeustadtWiener NeustadtAustria
  7. 7.Department of Thoracic SurgeryMedical University of ViennaViennaAustria
  8. 8.Department of SurgeryGeneral Hospital Wiener NeustadtWiener NeustadtAustria

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