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Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo

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Abstract

We have studied the gene expression pattern of invasive primary mammary tumor cells using a unique in vivo invasion assay that isolates the invasive tumor cells by chemotaxis. One of the genes upregulated in the invasive tumor cells is Mena, an actin binding protein involved in the regulation of cell motility. There are multiple known splice variants of Mena accounted for by four alternatively included exons, +, ++, +++ and 11a. Using the in vivo invasion assay in rats and mice with mammary tumors we observed that two isoforms of Mena, ++ and +++, are upregulated in the invasive tumor cells and one isoform, 11a, is downregulated. The Mena isoform switching pattern described here may provide a new biomarker for the presence of metastatic cancer cells and for prognosis.

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Acknowledgements

The authors wish to acknowledge Andrew Freidman for technical help, Drs Erik Sahai and Jeffrey Segall for their help in discussions. U.P. was supported by the Anna Fuller Molecular Oncology Fund and the Ludwig Center for Molecular Oncology. This work is supported by NIH CA 100324 (SG and JC) and CA113395 (JC), NIH grant # GM58801 and ICBP grant # 1-U54-CA112967 for FBG, Lega Italiana per la Lotta Contro i Tumori and Associazione Italiana per la Ricerca sul Cancro (AIRC) for PN. SG is the recipient of the Young Investigator Award from Breast Cancer Alliance Inc.

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Author notes

  1. Ulrike Philippar

    Present address: Merck Research Laboratories, Boston, MA, USA

  2. Weigang Wang

    Present address: ImClone Systems Incorporated, New York, NY, USA

Authors and Affiliations

  1. Department of Anatomy and Structural Biology, Albert Einstein College of Medicine of Yeshiva University, 1300 Morris Park Avenue, Bronx, NY, 10461, USA

    Sumanta Goswami, Daqian Sun, Antonia Patsialou, Weigang Wang & John S. Condeelis

  2. Department of Biology, Yeshiva University, New York, NY, USA

    Sumanta Goswami & Jacob Avraham

  3. Koch Institute for Integrative Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA

    Ulrike Philippar & Frank B. Gertler

  4. Laboratory of Experimental Chemotherapy, Regina Elena Cancer Institute, Rome, Italy

    Francesca Di Modugno

  5. Laboratory of Immunology, Regina Elena Cancer Institute, Rome, Italy

    Paola Nistico

Authors
  1. Sumanta Goswami
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  2. Ulrike Philippar
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Correspondence to Sumanta Goswami.

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Goswami, S., Philippar, U., Sun, D. et al. Identification of invasion specific splice variants of the cytoskeletal protein Mena present in mammary tumor cells during invasion in vivo. Clin Exp Metastasis 26, 153–159 (2009). https://doi.org/10.1007/s10585-008-9225-8

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