Recombinant human IFN-beta affects androgen receptor level, neuroendocrine differentiation, cell adhesion, and motility in prostate cancer cells.
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.
Angelucci
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C
Istituto di Istologia ed Embriologia, Facoltà di Medicina e Chirurgia, Università Cattolica del Sacro Cuore di Roma, 1 Largo Francesco Vito, 00168 Rome, Italy.
Iacopino
F
F
Ferracuti
S
S
Urbano
R
R
Sica
G
G
D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D006801:Humans; D016899:Interferon-beta / Q000627:therapeutic use*; D008297:Male; D009490:Neurosecretory Systems / Q000166:cytology* / Q000187:drug effects; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use*