Journal of Mammary Gland Biology and Neoplasia

, Volume 6, Issue 1, pp 67–82

TGF-β Signaling in Mammary Gland Development and Tumorigenesis

  • Lalage M. Wakefield
  • Ester Piek
  • Erwin P. Böttinger
Article

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.

TGF-βs signal transduction Smads MAP kinases breast cancer serine-threonine receptor kinases 

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Copyright information

© Plenum Publishing Corporation 2001

Authors and Affiliations

  • Lalage M. Wakefield
    • 1
  • Ester Piek
    • 1
  • Erwin P. Böttinger
    • 2
  1. 1.Laboratory of Cell Regulation and CarcinogenesisNational Cancer InstituteBethesda
  2. 2.Departments of Medicine and Molecular GeneticsAlbert Einstein College of MedicineBronx

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