Functional angiotensin II type 2 receptors inhibit growth factor signaling in LNCaP and PC3 prostate cancer cell lines

BACKGROUND. There is clear evidence of a tissue-based renin-angiotensin system in the prostate and studies to date suggest that AT(1)-receptor blocking drugs inhibit the growth of some prostate cancer cell lines and delay the development of prostate cancer. The present studies examine the action of Ang II in two prostate cancer cell lines and report the presence of functional AT(2)-receptors that regulate the actions of growth factors. METHODS. Immunohistochemistry was used to identify the presence of Ang II and QPCR techniques to examine AT(1)- and AT(2)-receptor mRNA expression in androgen-dependent (LNCaP) and independent (PC3) cell lines. The effects of AT(1)- and AT(2)-receptor activation upon EGF-induced DNA synthesis and ERK2 phosphorylation in these cells were also examined. RESULTS. Functional AT2-receptors together with Ang II were identified in both cell lines and stimulation of these receptors inhibited EGF-induced DNA synthesis and ERK2 phosphorylation. AT(1)-receptors, although present in both cell lines, were only functional in LNCaP cells where activation stimulated DNA synthesis. CONCLUSIONS. Functional AT2-receptors are present and have the capacity to inhibit EGF-induced prostate cancer cell growth in LNCaP and fast growing androgen-independent PC3 cell lines, whereas functional AT(1)-receptors are found only in LNCaP cells where their activation stimulates DNA synthesis.