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

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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.

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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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Authors and Affiliations

  1. Clinical Division of Oncology, Department of Medicine I, Medical University of Vienna, Währinger Gürtel 18-20, 1090, Vienna, Austria

    Gerwin Heller, Barbara Ziegler, Robert Pirker, Christoph C. Zielinski & Sabine Zöchbauer-Müller

  2. Center of Excellence in Clinical and Experimental Oncology, Medical University of Vienna, Vienna, Austria

    Gerwin Heller, Barbara Ziegler, Robert Pirker, Christoph C. Zielinski & Sabine Zöchbauer-Müller

  3. Department of Pathology, Duke University Medical Center, Durham, NC, USA

    Joseph Geradts

  4. Brain Tumor Center, Department of Neuro-Oncology, M. D. Anderson Cancer Center, Houston, TX, USA

    Irene Newsham

  5. Institute of Cancer Research, Medical University of Vienna, Vienna, Austria

    Martin Filipits & Walter Berger

  6. Department of Pathology, General Hospital Wiener Neustadt, Wiener Neustadt, Austria

    Eva-Maria Markis-Ritzinger & Wolfgang Stiglbauer

  7. Department of Thoracic Surgery, Medical University of Vienna, Vienna, Austria

    Daniela Kandioler

  8. Department of Surgery, General Hospital Wiener Neustadt, Wiener Neustadt, Austria

    Dieter Depisch

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  1. Gerwin Heller
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  2. Joseph Geradts
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  3. Barbara Ziegler
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  4. Irene Newsham
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  5. Martin Filipits
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  6. Eva-Maria Markis-Ritzinger
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  7. Daniela Kandioler
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  8. Walter Berger
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  9. Wolfgang Stiglbauer
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  10. Dieter Depisch
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  11. Robert Pirker
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  12. Christoph C. Zielinski
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  13. Sabine Zöchbauer-Müller
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Correspondence to Sabine Zöchbauer-Müller.

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Heller, G., Geradts, J., Ziegler, B. et al. Downregulation of TSLC1 and DAL-1 expression occurs frequently in breast cancer. Breast Cancer Res Treat 103, 283–291 (2007). https://doi.org/10.1007/s10549-006-9377-7

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  • DOI: https://doi.org/10.1007/s10549-006-9377-7

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