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Transforming Growth Factor-β in Cancer Therapy, Volume II pp 141–151Cite as

TGF-β and HER2/ErbB2 and Breast Cancer Progression

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Part of the book series: Cancer Drug Discovery and Development ((CDD&D))

Abstract

Breast cancer progression is a result of deregulated expression of several interrelated biomarkers. In that context, complex relations between transforming growth factor-β (TGF-β) and human epidermal growth factor receptor 2 (HER2) are under intensive investigation. HER2 seems to provide proliferative advantage to tumor cells, increasing their survival ability during clonal selection, and TGF-β provides greater invasiveness and metastatic potential to these cells, leading to a more aggressive phenotype of breast cancer. Paradoxical acting of TGF-β during breast cancer progression could be based on disruption of the balance between various signaling pathways, such as Smad and Ras/MAPK pathways which are involved in mediating the tumor suppressor and oncogenic effects of TGF-β. The Ras/MAPK pathway also seems to have a central role in the HER2 signaling network. Smad and Ras/MAPK pathways can interact at different levels and with different outcomes, depending on cellular context, and may either synergize or antagonize each other. That could be especially important in breast cancer progression, contributing to the unique biological outcomes. In that case, selective inactivation of the pathway that is more important for the suppressor effects will promote tumor development while leaving the oncogenic response intact. If corresponding clinical research shows that a synergistic relation does exist between elevated levels of TGF-β and overexpressed HER2, it could lead to improvement in therapeutic strategies for breast cancer patients.

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Authors and Affiliations

  1. Department of Experimental Oncology, Institute of Oncology and Radiology of Serbia, Belgrade, Serbia and Montenegro

    Nataša Todorović-Raković MSc

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  1. Nataša Todorović-Raković MSc
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Editors and Affiliations

  1. Cancer Training Branch, Office of Centers, Training and Resources, National Cancer Institute, Bethesda, MD

    Sonia B. Jakowlew PhD

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© 2008 Humana Press Inc., Totowa, NJ

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Todorović-Raković, N. (2008). TGF-β and HER2/ErbB2 and Breast Cancer Progression. In: Jakowlew, S.B. (eds) Transforming Growth Factor-β in Cancer Therapy, Volume II. Cancer Drug Discovery and Development. Humana Press. https://doi.org/10.1007/978-1-59745-293-9_10

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  • DOI: https://doi.org/10.1007/978-1-59745-293-9_10

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-715-0

  • Online ISBN: 978-1-59745-293-9

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