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Parallel inhibition of cell growth and induction of cell migration and invasion in breast cancer cells by bone morphogenetic protein 4

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Abstract

Bone morphogenetic proteins (BMP) are extracellular signaling molecules that belong to the transforming growth factor β (TGFβ) superfamily. Bone morphogenetic proteins have diverse roles during development where they regulate proliferation, differentiation, and apoptosis in many different cell types by modulating the transcription of specific target genes. BMPs have also been implicated in both promotion and inhibition of cancer progression. We have recently shown that BMP4 is commonly expressed in breast cancer but its functional significance has not been previously explored. Our data demonstrate that in all nine breast cancer cell lines studied, BMP4 treatment leads to a dramatic growth suppression as a result of the induction of G1 arrest of the cell cycle. At the same time, BMP4 stimulates cell migration and invasion in a subset of these breast cancer cell lines. The BMP4-induced phenotypic changes were mediated through the activation of the canonical SMAD signaling pathway whereas no activation of MAP-kinases ERK1/2 or p38 was detected. Our results thus implicate that BMP4 is an important regulator of key phenotypic characteristics of cancer cells, cell growth, cell migration, and invasion, and that, similar to TGFβ, it possesses both tumor suppressive and oncogenic properties in breast cancer.

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Acknowledgments

The authors greatly appreciate the skillful assistance of Ms. Kati Rouhento. This study was partly supported by grants from The Sigrid Juselius Foundation, The Medical Research Fund of the Tampere University Hospital, and the Finnish Cancer Organizations.

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Authors and Affiliations

  1. Laboratory of Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, 33014, Tampere, Finland

    Johanna M. Ketolainen, Emma-Leena Alarmo & Anne Kallioniemi

  2. Laboratory of Cancer Biology, Institute of Medical Technology, University of Tampere, Tampere, Finland

    Vilppu J. Tuominen

Authors
  1. Johanna M. Ketolainen
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  2. Emma-Leena Alarmo
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  3. Vilppu J. Tuominen
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  4. Anne Kallioniemi
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Correspondence to Anne Kallioniemi.

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Supplemental Fig. 1

BMP4 treatment does not induce epithelial-mesenchymal transition. Cells were treated with BMP4 (100 ng/ml) or vehicle for three days and then the E-cadherin and vimentin mRNA levels were measured using RT-PCR (32 kb)

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Ketolainen, J.M., Alarmo, EL., Tuominen, V.J. et al. Parallel inhibition of cell growth and induction of cell migration and invasion in breast cancer cells by bone morphogenetic protein 4. Breast Cancer Res Treat 124, 377–386 (2010). https://doi.org/10.1007/s10549-010-0808-0

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  • DOI: https://doi.org/10.1007/s10549-010-0808-0

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