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TGF-β Signaling in Mammary Gland Development and Tumorigenesis

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Abstract

Ligands of the TGF-β superfamily are unique in that they signal through transmembrane receptor serine-threonine kinases, rather than tyrosine kinases. The receptor complex couples to a signal transduction pathway involving a novel family of proteins, the Smads. On phosphorylation, Smads translocate to the nucleus where they modulate transcriptional responses. However, TGF-βs can also activate the mitogen-activated protein kinase (MAPK)4 pathway, and the different biological responses to TGF-β depend to varying degrees on activation of either or both of these two pathways. The Smad pathway is a nexus for cross-talk with other signal transduction pathways and for modulation by many different interacting proteins. Despite compelling evidence that TGF-β has tumor suppressor activity in the mammary gland, neither TGF-β receptors nor Smads are genetically inactivated in human breast cancer, though receptor expression is reduced. Possible reasons are discussed in relation to the dual role of TGF-β as tumor suppressor and oncogene.

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Authors and Affiliations

  1. Laboratory of Cell Regulation and Carcinogenesis, National Cancer Institute, Bethesda, Maryland

    Lalage M. Wakefield & Ester Piek

  2. Departments of Medicine and Molecular Genetics, Albert Einstein College of Medicine, Bronx, New York

    Erwin P. Böttinger

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Wakefield, L.M., Piek, E. & Böttinger, E.P. TGF-β Signaling in Mammary Gland Development and Tumorigenesis. J Mammary Gland Biol Neoplasia 6, 67–82 (2001). https://doi.org/10.1023/A:1009568532177

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