Recombinant human IFN-beta affects androgen receptor level, neuroendocrine differentiation, cell adhesion, and motility in prostate cancer cells

J Interferon Cytokine Res. 2007 Aug;27(8):643-52. doi: 10.1089/jir.2006.0120.


We provide evidence that recombinant human interferon-beta (rHuIFN-beta) is able to increase androgen receptor (AR) expression, interfere with the acquisition of a neuroendocrine (NE) phenotype, and improve adhesion potential of androgen-insensitive prostate cancer cells (PC-3). The effect of rHuIFN-beta (10-1000 IU/mL) on AR, chromogranin A (CgA), E-cadherin (E-cad), N-cadherin (N-cad), and c-met levels was investigated by Western blotting after 48, 96, and 144 h. In agreement with our previous results, rHuIFN-beta (10-1000 IU/mL) induced a dramatic increase in AR (up to 5.3-fold, p < 0.001) that was already evident with the lowest cytokine concentration (10 IU/mL). A reduction in CgA levels (up to 45%, p < 0.002) was produced by 100 and 1000 IU/mL after 48-144 h. E-cad upregulation (up to 90%, p < 0.05) was observed starting from 96 h of treatment with 100 and 1000 IU/mL rHuIFN-beta and persisted until 144 h. An rHuIFN-beta-dependent reduction occurred in N-cad and c-met signal after a 48-96 h of treatment. This effect was particularly strong after 144 h of exposure to 1000 IU/mL rHuIFN-beta (81.5%, N-cad; 58%, c-met) (p < 0.002). Reverse transcription-PCR (RT-PCR) analysis of c-met expression demonstrated that the IFN-induced c-met downregulation mostly occurs at the transcriptional level (reduction up to nearly 50%, p < 0.000). Together, these results indicate that rHuIFN-beta may reduce the motility and invasiveness of poorly differentiated prostate cancer cells and interfere with the acquisition of an NE phenotype, often characterized by a low AR level.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cell Movement / drug effects*
  • Humans
  • Interferon-beta / therapeutic use*
  • Male
  • Neurosecretory Systems / cytology*
  • Neurosecretory Systems / drug effects
  • Prostatic Neoplasms / drug therapy*
  • Prostatic Neoplasms / metabolism
  • Prostatic Neoplasms / pathology
  • Receptors, Androgen / metabolism*
  • Recombinant Proteins / therapeutic use*


  • Receptors, Androgen
  • Recombinant Proteins
  • Interferon-beta