Prostate-derived factor as a paracrine and autocrine factor for the proliferation of androgen receptor-positive human prostate cancer cells

Prostate. 2007 Apr 1;67(5):557-71. doi: 10.1002/pros.20551.


Background: The expression of prostate-derived factor (PDF) is significantly elevated in human prostate tumors. We investigate the functional role and signaling of PDF in androgen receptor (AR)-positive human prostate cancer cells.

Methods: Transient or stable expression of PDF by cDNA transfection, antisense-mediated gene silencing, media conditioned by PDF-elevated cells, and antibody (Ab) neutralization were employed.

Results: Elevated endogenous and exogenous expression of PDF and treatment of PDF-enriched media were associated with increased proliferation and clonogenic growth of the cells. On the contrary, knockdown of PDF or addition of PDF neutralizing Ab resulted in diminished proliferation and reduced anchorage-independent growth. Further, ERK1/2 and p90RSK, but not Smad2/3, were activated in PDF-elevated cells as well as in cells treated with PDF-enriched media, while inhibition of ERK1/2 decreased the growth of those cells.

Conclusion: PDF promotes AR-positive prostate tumor progression through upregulating cell proliferation via ERK1/2 signal pathway.

Publication types

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

MeSH terms

  • Blotting, Western
  • Bone Morphogenetic Proteins / biosynthesis*
  • Bone Morphogenetic Proteins / genetics
  • Bone Morphogenetic Proteins / metabolism
  • Cell Adhesion / physiology
  • Cell Growth Processes / physiology
  • Cell Line, Tumor
  • Gene Silencing
  • Growth Differentiation Factor 15
  • Humans
  • Male
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Prostatic Neoplasms / genetics
  • Prostatic Neoplasms / metabolism*
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / biosynthesis*
  • Ribosomal Protein S6 Kinases, 90-kDa / metabolism
  • Signal Transduction
  • Transfection
  • Transforming Growth Factor beta / metabolism


  • AR protein, human
  • Bone Morphogenetic Proteins
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • Receptors, Androgen
  • Transforming Growth Factor beta
  • Ribosomal Protein S6 Kinases, 90-kDa
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3