Sex steroid hormones act as growth factors

J Steroid Biochem Mol Biol. 2002 Dec;83(1-5):31-5. doi: 10.1016/s0960-0760(02)00264-9.


We observed that sex steroid hormones, like growth factors, stimulate the Src/Ras/erk pathway of cell lines derived from human mammary or prostate cancers. In addition, hormone-dependent pathway activation can be induced in Cos cells, upon transfection of classic steroid receptors. Cross-talks between sex steroid receptors regulate their association with Src and consequent pathway activation. Oestradiol treatment of MCF-7 cells triggers simultaneous association of ER with Src and p85, the regulatory subunit of phosphatidylinositol-3-kinase (PI3-kinase) and activation of Src- and PI3-K-dependent pathways. Activation of the latter pathway triggers cyclin D1 transcription, that is unaffected by Mek-1 activation. This suggests that simultaneous activation of different signalling effectors is required to target different cell cycle components. Thus, a novel reciprocal cross-talk between the two pathways appears to be mediated by the ER. In all tested cells, activation of the signalling pathways has a proliferative role. Transcriptionally inactive ER expressed in NIH 3T3 cells responds to hormone causing Src/Ras/Erk pathway activation and DNA synthesis. This suggests that in these cells genomic activity is required for later events of cell growth.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • 3T3 Cells
  • Animals
  • CSK Tyrosine-Protein Kinase
  • Cell Division
  • Cyclin D1 / metabolism
  • DNA / biosynthesis
  • Estradiol / metabolism
  • Estradiol / pharmacology
  • Estrogen Receptor Modulators / pharmacology
  • Gonadal Steroid Hormones / metabolism*
  • Growth Substances / metabolism*
  • Humans
  • Mice
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein-Tyrosine Kinases / metabolism
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Signal Transduction
  • Time Factors
  • Transcription, Genetic
  • Transcriptional Activation
  • Tumor Cells, Cultured
  • src-Family Kinases


  • Estrogen Receptor Modulators
  • Gonadal Steroid Hormones
  • Growth Substances
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Cyclin D1
  • Estradiol
  • DNA
  • Protein-Tyrosine Kinases
  • CSK Tyrosine-Protein Kinase
  • src-Family Kinases
  • CSK protein, human