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  • Original Paper
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Expression profiling of epithelial plasticity in tumor progression

Oncogene volume 22, pages 7155–7169 (2003)Cite this article

Abstract

Epithelial-to-mesenchymal transition (EMT), a switch of polarized epithelial cells to a migratory, fibroblastoid phenotype, is increasingly considered as an important event during malignant tumor progression and metastasis. To identify molecular players involved in EMT and metastasis, we performed expression profiling of a set of combined in vitro/in vivo cellular models, based on clonal, fully polarized mammary epithelial cells. Seven closely related cell pairs were used, which were modified by defined oncogenes and/or external factors and showed specific aspects of epithelial plasticity relevant to cell migration, local invasion and metastasis. Since mRNA levels do not necessarily reflect protein levels in cells, we used an improved expression profiling method based on polysome-bound RNA, suitable to analyse global gene expression on Affymetrix chips. A substantial fraction of all regulated genes was found to be exclusively controlled at the translational level. Furthermore, profiling of the above multiple cell pairs allowed one to identify small numbers of genes by cluster analysis, specifically correlating gene expression with EMT, metastasis, scattering and/or oncogene function. A small set of genes specifically regulated during EMT was identified, including key regulators and signaling pathways involved in cell proliferation, epithelial polarity, survival and trans-differentiation to mesenchymal-like cells with invasive behavior.

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Acknowledgements

We thank G Wirl for providing us with the tenascin C antibody. We also thank G Loeber, E Müllner and M Huber for advice and comments on the manuscript, K Quast, A Köhler, K Fiesel for bioinformatics support, and G Litos, W Rust, E Brickl, D Knebel, A Ackermann and A Fischbach for expert technical assistance. Finally, we are particularly grateful to A Eger and R Foisner for help with comparing TGFβ1/3 mRNA and protein expression in FosER cells. This work was supported by grants from an EU TMR network (ERBFMRXCT-980197), from the Austrian Research funding agency (FWF; SFB 006/612) and the Austrian Industrial Research Promotion Fund (FFF project No. 803776).

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Author notes

  1. Norbert Kraut

    Present address: Boehringer Ingelheim Austria GmbH, Department of NCE Lead Discovery, Dr Boehringer Gasse 5-11, Vienna, A 1121, Austria

  2. Martin Jechlinger

    Present address: Memorial Sloan Kettering Cancer Center, 1275 York Ave, Box 62, New York, NY, 10021, USA

  3. Elzbieta Janda

    Present address: European Patent Office Munich, Erhardtstrsse 27, 80331, Munich, Germany

  4. Susanna Lüdemann

    Present address: Dipartimento di Medicina Sperimentale e Clinica Universita degli studi Magna Graecia, Policlinico Mater Domini Piano 5, Via Campanella 115, 88100, Catanzaro, Italy

  5. Hartmut Beug and Norbert Kraut: These two authors contributed equally to this work

Authors and Affiliations

  1. IMP, Research Institute for Molecular Pathology, Dr Bohrgasse 7, Vienna, A-1030, Austria

    Martin Jechlinger, Stefan Grunert, Ido H Tamir, Elzbieta Janda, Susanna Lüdemann, Thomas Waerner & Hartmut Beug

  2. Boehringer Ingelheim Pharma KG, Genomics Group, Birkendorfer Str. 65, Biberach, D-88397, Germany

    Peter Seither, Andreas Weith & Norbert Kraut

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  1. Martin Jechlinger
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Correspondence to Hartmut Beug.

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Jechlinger, M., Grunert, S., Tamir, I. et al. Expression profiling of epithelial plasticity in tumor progression. Oncogene 22, 7155–7169 (2003). https://doi.org/10.1038/sj.onc.1206887

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  • DOI: https://doi.org/10.1038/sj.onc.1206887

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