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.