Expression levels of the putative zinc transporter LIV-1 are associated with a better outcome of breast cancer patients†
Corresponding Author
Grit Kasper
Center for Musculoskeletal Surgery, Charité-University Medicine Berlin, Berlin, Germany
Fax: +0049-30-450525956, +0049-30-450559969.
Center for Musculoskeletal Surgery, Charité-University Medicine Berlin, Free and Humboldt-University of Berlin, Campus Virchow-Clinic, Augustenburger Platz 1, D-13353 Berlin, GermanySearch for more papers by this authorArmin A. Weiser
Institute of Biochemistry, Charité-University Medicine Berlin, Berlin, Germany
Search for more papers by this authorAndreas Rump
Institute of Medical Genetics, Technical University, Dresden, Germany
Search for more papers by this authorEdgar Dahl
Institute of Pathology, University Hospital of RWTH Aachen, Aachen, Germany
Search for more papers by this authorArndt Hartmann
Institute of Pathology, University of Regensburg, Regensburg, Germany
Search for more papers by this authorPeter Wild
Institute of Pathology, University of Regensburg, Regensburg, Germany
Search for more papers by this authorEsmeralda Castaños-Vélez
Signature Diagnostics AG, Berlin, Germany
Search for more papers by this authorKerstin Lehmann
Center for Cardiovascular Research, Charité-University Medicine Berlin, Berlin, Germany
Search for more papers by this authorCorresponding Author
Grit Kasper
Center for Musculoskeletal Surgery, Charité-University Medicine Berlin, Berlin, Germany
Fax: +0049-30-450525956, +0049-30-450559969.
Center for Musculoskeletal Surgery, Charité-University Medicine Berlin, Free and Humboldt-University of Berlin, Campus Virchow-Clinic, Augustenburger Platz 1, D-13353 Berlin, GermanySearch for more papers by this authorArmin A. Weiser
Institute of Biochemistry, Charité-University Medicine Berlin, Berlin, Germany
Search for more papers by this authorAndreas Rump
Institute of Medical Genetics, Technical University, Dresden, Germany
Search for more papers by this authorEdgar Dahl
Institute of Pathology, University Hospital of RWTH Aachen, Aachen, Germany
Search for more papers by this authorArndt Hartmann
Institute of Pathology, University of Regensburg, Regensburg, Germany
Search for more papers by this authorPeter Wild
Institute of Pathology, University of Regensburg, Regensburg, Germany
Search for more papers by this authorEsmeralda Castaños-Vélez
Signature Diagnostics AG, Berlin, Germany
Search for more papers by this authorKerstin Lehmann
Center for Cardiovascular Research, Charité-University Medicine Berlin, Berlin, Germany
Search for more papers by this authorParts of our study were conducted at metaGen Pharmaceuticals GmbH, Berlin, Germany.
Abstract
We investigated the expression pattern of the breast cancer associated gene LIV-1 on mRNA and protein level in 111 human breast cancer patients by in situ hybridization as well as immunohistochemistry and focused on the unknown potential of LIV-1 expression levels as a prognostic marker. To our knowledge, this is the first study on endogenous LIV-1 protein expression. Results of our study indicate that LIV-1 mRNA and protein expression levels are only weakly correlated, suggesting posttranscriptional regulatory mechanisms. Furthermore, LIV-1 mRNA quantity in combination with a positive ER status seem to represent a better marker than the progesterone receptor status according to the prognostic significance for relapse free survival (RFS). A negative correlation of LIV-1 protein levels with tumor size, grade and stage reflects an association of LIV-1 protein expression with less aggressive tumors. High LIV-1 protein expression seems to be associated with a longer relapse free and overall survival in breast cancer patients with invasive ductal carcinoma. This association, however, seems to be dependent from other prognostic markers. Our data suggest that LIV-1 is a promising candidate for a novel marker for breast cancer patients with better outcome. Furthermore, our study presents a revised cDNA sequence of LIV-1 and demonstrates the localization of endogenous LIV-1 in the endoplasmic reticulum. (Supplementary material for this article can be found on the International Journal of Cancer website at http://www.interscience. wiley.com/jpages/0020-7136/suppmat/index.html). © 2005 Wiley-Liss, Inc.
Supporting Information
| Filename | Description |
|---|---|
| jwsIJCv117.kasper.tbl1.pdf25.3 KB | Evaluation of the Prognostic Significance of LIV-1 protein Expression for RFS in Different Patient Subgroups |
| jwsIJCv117.kasper.tbl2.pdf22.4 KB | Evaluation of the Prognostic Significance of LIV-1 Protein Expression Level for RFS in IDCS Using Different Cut Off Points |
| jwsIJCv117.kasper.fig1.pdf97.3 KB | LIV-1 protein expression levels are not dependent on the ER in breast cell lines. Cell lysates from different breast cell lines were analyzed by Western blotting using the antibody LIV-1a. All cell lines show a band at the expected molecular weight of LIV-1 (85 kDA). There are no prominent changes in the endogenous LIV-1 protein level, regardless if the cell line is ER1 (e.g., ZR- 75-1) or ER2 (e.g., MDA-MB-231) or derived from normal breast tissue (MCF-10A). |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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