Inhibition of the epidermal growth factor receptor enhances castration‐induced prostate involution and reduces testosterone‐stimulated prostate growth in adult rats

Abstract

This study suggests that increased EGFR signaling during castration mediates stimulatory effects balancing castration-induced prostate regression, and that EGFR signaling is a necessary component in testosterone-stimulated prostate growth.

Epidermal growth factor receptor expression escapes androgen regulation in prostate cancer: a potential molecular switch for tumour growth

“…Inhibition of EGFR signalling with antibody blockade after castration led to a further reduction in epithelial and blood vessel weight. The authors suggested that inhibition of EGFR signalling in castrated animals resulted in rapid prostate involution (Hammarsten et al, 2007). These data support the hypothesis that androgens downregulate EGFR expression in normal prostate tissue (Traish and Wotiz, 1987;St-Arnaud et al, 1988;Nishi et al, 1996).…”

“…These results suggested that castration-induced increase in EGFR expression may be needed to counterbalance the loss of androgen-stimulated growth and to prevent complete tissue involution (Hammarsten et al, 2007). Interestingly, EGFR signalling is inhibited during testosterone-induced growth, which led to growth reduction and prevented excessive proliferation.…”

“…Recent studies also reported that androgen treatment of castrated animals reduced EGFR protein density, diminished epithelial and endothelial cell proliferation, and increased epithelial cell apoptosis (Hammarsten et al, 2007). These results suggested that castration-induced increase in EGFR expression may be needed to counterbalance the loss of androgen-stimulated growth and to prevent complete tissue involution (Hammarsten et al, 2007).…”

“…Among the specific target genes that are downregulated by androgen in normal prostate tissue is the EGFR. Regulation of EGFR expression by androgens is shown to be at the transcriptional level, both in normal prostate tissue and prostate cancer (PCa) cell lines (Brass et al, 1995;Ravenna et al, 1995;Nishi et al, 1996;Itoh et al, 1998;Schwartz et al, 1998;Hammarsten et al, 2007;Pignon et al, 2009). This regulation seems to be negatively regulated in normal cells and upregulated in PCa, especially in androgen-independent PCa.…”

“…These signalling pathways may activate the AR without ligand, culminating in androgenreceptor signalling, leading to cellular proliferation, migration, and survival. The references for the reactions cited in Figure 1 are as follows: Reaction 1, Heinlein and Chang, 2004; Reaction 2, Heinlein and Chang, 2004;Reaction 3, Heinlein and Chang, 2004;Reaction 4, Heinlein and Chang, 2004;Reaction 5, Heinlein and Chang, 2004;Reaction 6, Heinlein and Chang, 2004;Reaction 7, Brass et al, 1995;Ravenna et al, 1995;Itoh et al, 1998;Schwartz et al, 1998;Heinlein and Chang, 2004;Hammarsten et al, 2007;Pignon et al, 2009;Reaction 8, Nishi et al, 1996;Reaction 9, Traish and Wotiz, 1987;St-Arnaud et al, 1988;Reaction 10, Sugita et al, 2004;Gregory et al, 2005;Migliaccio et al, 2006;Léotoing et al, 2007;Zhu and Kyprianou, 2008;Recchia et al, 2009;Reaction 11, Migliaccio et al, 2006;Léotoing et al, 2007;Zhu and Kyprianou, 2008;Recchia et al, 2009;Reaction 12, Migliaccio et al, 2006;Léotoing et al, 2007;Zhu and Kyprianou, 2008;Recchia et al, 2009;Reaction 13, Migliaccio et al, 2006;Léotoing et al, 2007;Zhu and Kyprianou, 2008;Recchia et al, 2009;Reaction 14, Migliaccio et al, 2006;Léotoing et al, 2007;Zhu and Kyprianou, 2008;Recchia et al, 2009. Abbreviations: AKT, protein kinase B; AR, androgen receptor; ARE, androgen response element; 5a-DHT, d...…”