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Journal of Cellular Biochemistry

Leptin signaling in breast cancer: An overview

Authors

  • Donatella Cirillo,

    1. Protein Chemistry Laboratory, Centro di Ricerche Oncologiche di Mercogliano—CROM, Mercogliano (AV), Italy
    2. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia
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  • Anna Maria Rachiglio,

    1. Cell Biology Laboratory, Centro di Ricerche Oncologiche di Mercogliano—CROM, Mercogliano (AV), Italy
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  • Raffaele la Montagna,

    1. Human Health Foundation, Spoleto (PG), Italy
    2. Department of Human Pathology and Oncology, University of Siena, Siena, Italy
    3. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia
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  • Antonio Giordano,

    1. Protein Chemistry Laboratory, Centro di Ricerche Oncologiche di Mercogliano—CROM, Mercogliano (AV), Italy
    2. Department of Human Pathology and Oncology, University of Siena, Siena, Italy
    3. Sbarro Institute for Cancer Research and Molecular Medicine, Center for Biotechnology, Temple University, Philadelphia
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  • Nicola Normanno

    Corresponding author
    1. Cell Biology Laboratory, Centro di Ricerche Oncologiche di Mercogliano—CROM, Mercogliano (AV), Italy
    2. Cell Biology and Biotherapy Unit, INT-Fondazione Pascale, Naples, Italy
    • Cell Biology and Biotherapy Unit, INT-Fondazione Pascale, 80131 Naples, Italy.
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Abstract

The adipocyte-derived peptide leptin acts through binding to specific membrane receptors, of which six isoforms (obRa-f) have been identified up to now. Binding of leptin to its receptor induces activation of different signaling pathways, including the JAK/STAT, MAPK, IRS1, and SOCS3 signaling pathways. Since the circulating levels of leptin are elevated in obese individuals, and excess body weight has been shown to increase breast cancer risk in postmenopausal women, several studies addressed the role of leptin in breast cancer. Expression of leptin and its receptors has been demonstrated to occur in breast cancer cell lines and in human primary breast carcinoma. Leptin is able to induce the growth of breast cancer cells through activation of the Jak/STAT3, ERK1/2, and/or PI3K pathways, and can mediate angiogenesis by inducing the expression of vascular endothelial growth factor (VEGF). In addition, leptin induces transactivation of ErbB-2, and interacts in triple negative breast cancer cells with insulin like growth factor-1 (IGF-1) to transactivate the epidermal growth factor receptor (EGFR), thus promoting invasion and migration. Leptin can also affect the growth of estrogen receptor (ER)-positive breast cancer cells, by stimulating aromatase expression and thereby increasing estrogen levels through the aromatization of androgens, and by inducing MAPK-dependent activation of ER. Taken together, these findings suggest that the leptin system might play an important role in breast cancer pathogenesis and progression, and that it might represent a novel target for therapeutic intervention in breast cancer. J. Cell. Biochem. 105: 956–964, 2008. © 2008 Wiley-Liss, Inc.

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