Long-term presence of androgens and anti-androgens modulate EGF-receptor expression and MAP-kinase phosphorylation in androgen receptor-prostate positive cancer cells

  • Authors:
    • Giovanni Luca Gravina
    • Claudio Festuccia
    • Adriano Angelucci
    • Angelo Poletti
    • Daila Capuano
    • Carlo Vicentini
    • Marcella Motta
    • Mauro Bologna
  • View Affiliations

  • Published online on: July 1, 2004     https://doi.org/10.3892/ijo.25.1.97
  • Pages: 97-104
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

Prostate cancer (Pca) progression from an androgen-dependent to an androgen-independent state occurs in patients who undergo hormonal therapy. There is evidence indicating that deregulation of the epidermal growth factor receptor (EGFR) pathway plays a critical role in this phenomenon. In this study we addressed the question by stably transfecting the androgen receptor (AR) cDNA into the AR-negative Pca cell line DU145 that expresses high levels of EGFR. The resulting cell line has been named DU145-AR. We showed that the introduction of the AR restored positive androgen regulation of tumour cell growth and gene expression in vitro. The DU145-AR cells grown in culture medium containing androgens exhibited a transient up-regulation of EGFR levels with a subsequent down-regulation. This phenomenon was reversible, upon addition of hydroxiflutamide (HF) to the culture medium, but after prolonged treatment. When the EGFR repression is relieved in the presence of HF, the cells become more responsive either to EGF mediated growth or to anti-proliferative effect of PKI166, an inhibitor of EGFR phosphorylation. Moreover, we found a significant increase of the activated form of mitogen-activated-protein kinase (MAPK) in cells treated with HF. PKI166 blocked this HF mediated-MAPK activation, suggesting that the activation of MAPK is an event dependent on EGFR function. Our data demonstrate that hormone sensitive Pca cells possess a mechanism able to limit EGFR expression. Up-regulation of EGFR in response to long-term HF treatment could represent an attempt to rescue cell growth through a compensatory survival pathway.

Related Articles

Journal Cover

July 2004
Volume 25 Issue 1

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
x
Spandidos Publications style
Gravina GL, Festuccia C, Angelucci A, Poletti A, Capuano D, Vicentini C, Motta M and Bologna M: Long-term presence of androgens and anti-androgens modulate EGF-receptor expression and MAP-kinase phosphorylation in androgen receptor-prostate positive cancer cells. Int J Oncol 25: 97-104, 2004
APA
Gravina, G.L., Festuccia, C., Angelucci, A., Poletti, A., Capuano, D., Vicentini, C. ... Bologna, M. (2004). Long-term presence of androgens and anti-androgens modulate EGF-receptor expression and MAP-kinase phosphorylation in androgen receptor-prostate positive cancer cells. International Journal of Oncology, 25, 97-104. https://doi.org/10.3892/ijo.25.1.97
MLA
Gravina, G. L., Festuccia, C., Angelucci, A., Poletti, A., Capuano, D., Vicentini, C., Motta, M., Bologna, M."Long-term presence of androgens and anti-androgens modulate EGF-receptor expression and MAP-kinase phosphorylation in androgen receptor-prostate positive cancer cells". International Journal of Oncology 25.1 (2004): 97-104.
Chicago
Gravina, G. L., Festuccia, C., Angelucci, A., Poletti, A., Capuano, D., Vicentini, C., Motta, M., Bologna, M."Long-term presence of androgens and anti-androgens modulate EGF-receptor expression and MAP-kinase phosphorylation in androgen receptor-prostate positive cancer cells". International Journal of Oncology 25, no. 1 (2004): 97-104. https://doi.org/10.3892/ijo.25.1.97