Stromally expressed c-Jun regulates proliferation of prostate epithelial cells

Am J Pathol. 2007 Oct;171(4):1189-98. doi: 10.2353/ajpath.2007.070285. Epub 2007 Aug 16.


Stromal-epithelial interactions play a critical role in development of benign prostatic hyperplasia. We have previously shown that stromal cells associated with prostatic carcinoma can potentiate proliferation and reduce cell death of prostatic epithelial cells. Genetic alterations in stromal cells affect stromal-epithelial interactions and modulate epithelial growth. The c-Jun proteins that are early transcription factor molecules have been shown to regulate stromal-epithelial interactions via paracrine signals. Moreover, the Jun-family member proteins have been shown to play an important role in proper development of the genitourinary organs. In this study, we show that c-Jun protein in fibroblasts regulates production and paracrine signals of insulin-like growth factor-1 (IGF-1). c-jun(+/+) fibroblasts secrete higher levels of IGF-1 and stimulate benign prostatic hyperplasia-1 cellular proliferation. In addition, stromally produced IGF-1 up-regulates epithelial mitogen-activated protein kinase, Akt, and cyclin D protein levels while down-regulating the cyclin-dependent kinase inhibitor p27. These data suggest that stromally expressed c-Jun may promote prostatic epithelial proliferation through IGF-1 as a paracrine signal that, in turn, can promote prostate epithelial proliferation. Identification of the signal transduction pathways between prostate epithelial cells and the surrounding stromal cells will improve our understanding of the normal and abnormal biology in prostatic diseases.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Proliferation
  • Cyclin D
  • Cyclins / genetics
  • Cyclins / metabolism
  • Epithelial Cells / metabolism
  • Epithelial Cells / pathology
  • Fibroblasts / metabolism
  • Fibroblasts / pathology
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism*
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism
  • Male
  • Mitogen-Activated Protein Kinase Kinases / genetics
  • Mitogen-Activated Protein Kinase Kinases / metabolism
  • Oncogene Protein v-akt / genetics
  • Oncogene Protein v-akt / metabolism
  • Phosphatidylinositol 3-Kinases / genetics
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prostate / metabolism*
  • Prostate / pathology
  • Prostatic Hyperplasia / etiology*
  • Prostatic Hyperplasia / metabolism
  • Prostatic Hyperplasia / pathology*
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / metabolism*
  • Receptor, IGF Type 1 / genetics
  • Receptor, IGF Type 1 / metabolism
  • Stromal Cells / metabolism
  • Stromal Cells / pathology


  • Cyclin D
  • Cyclins
  • Intercellular Signaling Peptides and Proteins
  • Proto-Oncogene Proteins c-jun
  • Insulin-Like Growth Factor I
  • Phosphatidylinositol 3-Kinases
  • Receptor, IGF Type 1
  • Oncogene Protein v-akt
  • Mitogen-Activated Protein Kinase Kinases