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Breast cancer growth inhibition by delivery of the MDGI-derived peptide P108

Oncogene volume 19, pages 2455–2460 (2000)Cite this article

Abstract

Mammary derived growth inhibitor (MDGI) is a member of the family of cytoplasmic fatty acid binding proteins (FABPs), which bind hydrophobic ligands such as fatty acids, retinoids, eicosanoids and prostaglandines. MDGI and an 11 amino acid MDGI-derived conserved C-terminal peptide (P108) inhibits growth of normal mammary epithelial cells in tissue and organ culture, but fails to inhibit proliferation of many breast cancer cell lines in vitro. Here, the effects of peptide P108 on tumor growth of MCF-7, MDA-MB468 and MDA-MB231 human breast cancer cell lines in nude mice were tested. To deliver P108 into tumors, a novel peptide production system was applied for expression and secretion of small bioactive peptides in mammalian cells. Functional differentiation was observed in MCF-7 and MDA-MB468 cells upon P108 expression. In addition, EGF-dependent colony formation in soft agar by MDA-MB468 cells was inhibited by secreted P108. Tumor growth in athymic nude mice was suppressed in all three cell lines tested. Furthermore, P108 expressed by MCF-7/P108 cells caused paracrine tumor growth inhibition of MDA-MB231 cells. These results indicate that breast cancer inhibition by P108 is independent of binding to hydrophobic ligands and is perhaps mediated by interference with EGF-dependent signaling pathways.

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Acknowledgements

We thank Dr Dennis Shields for providing a cDNA for pre-prosomatostatin and antibody to the pre-pro-protein. We thank Dr David Salomon for giving us the β-casein antibody. We are very grateful to Dr Anton Wellstein and Dr Anna Tate-Riegel for providing conceptual input on the peptide delivery construct and for their continuous support and helpful discussions. We also wish to thank Dr Richard Grosse for his support of the project and critical reading of the manuscript.

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  1. Huey-Ling Wang

    Present address: Division of Biologics, Center for Drug Evaluation, 9F No. 9, Roosevelt Rd., Taipei, Taiwan

Authors and Affiliations

  1. Department of Pharmacology, Georgetown University, Vincent T. Lombardi Cancer Center, TRB W208, 3970 Reservoir Rd. NW, Washington, D.C. 20007, USA

    Huey-Ling Wang & Andreas Kurtz

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  1. Huey-Ling Wang
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  2. Andreas Kurtz
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Wang, HL., Kurtz, A. Breast cancer growth inhibition by delivery of the MDGI-derived peptide P108. Oncogene 19, 2455–2460 (2000). https://doi.org/10.1038/sj.onc.1203575

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