Integration of steroid and growth factor pathways in breast cancer: focus on signal transducers and activators of transcription and their potential role in resistance

Mol Endocrinol. 2007 Jul;21(7):1499-512. doi: 10.1210/me.2007-0109. Epub 2007 Apr 24.

Abstract

The signaling pathways that are critical to the development and growth of breast cancer include those activated downstream of the estrogen receptor (ER) and the human epidermal growth factor receptor family. Many of these pathways, including the signal transducer and activator of transcription pathway, are common to both. The well-described genomic actions of ER involve its role as a transcription factor, either by binding directly to DNA through estrogen response elements, or by tethering to DNA through interaction with other proteins. Nongenomic signaling by the ER involves interaction with membrane-associated signaling proteins such as the c-Src tyrosine kinase and adapter proteins p130Cas and moderator of nongenomic activity of ER. Interactions with the signal transducer and activator of transcription pathway are important in both ER signaling pathways and are critical for estrogen-induced proliferation and tumorigenesis. These mechanisms of signaling cross talk and their role in resistance to antiestrogen therapies are discussed.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / drug therapy
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Drug Resistance, Neoplasm
  • Epidermal Growth Factor / genetics
  • Epidermal Growth Factor / metabolism
  • Estrogen Receptor Modulators / therapeutic use
  • Female
  • Growth Substances / genetics
  • Growth Substances / metabolism
  • Humans
  • Mammary Neoplasms, Experimental / drug therapy
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / metabolism
  • Mice
  • Models, Biological
  • Receptors, Estrogen / genetics
  • Receptors, Estrogen / metabolism
  • STAT Transcription Factors / genetics
  • STAT Transcription Factors / metabolism
  • Signal Transduction
  • Steroids / metabolism
  • Transcription, Genetic

Substances

  • Estrogen Receptor Modulators
  • Growth Substances
  • Receptors, Estrogen
  • STAT Transcription Factors
  • Steroids
  • Epidermal Growth Factor