Chow L, Rezmann L, Imamura K, Wang L, Catt K, Tikellis C, Louis W J, Frauman A G, Louis S N S
Department of Medicine, The University of Melbourne, Austin Health, Heidelberg, Victoria, Australia.
Prostate. 2008 May 1;68(6):651-60. doi: 10.1002/pros.20738.
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.
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.
Functional AT(2)-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.
Functional AT(2)-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.
有明确证据表明前列腺中存在基于组织的肾素-血管紧张素系统，并且迄今为止的研究表明，AT(1)受体阻断药物可抑制某些前列腺癌细胞系的生长并延缓前列腺癌的发展。本研究检测了血管紧张素II（Ang II）在两种前列腺癌细胞系中的作用，并报告了调节生长因子作用的功能性AT(2)受体的存在。
采用免疫组织化学法鉴定Ang II的存在，并用定量聚合酶链反应（QPCR）技术检测雄激素依赖性（LNCaP）和非依赖性（PC3）细胞系中AT(1)和AT(2)受体mRNA的表达。还检测了AT(1)和AT(2)受体激活对这些细胞中表皮生长因子（EGF）诱导的DNA合成和细胞外信号调节激酶2（ERK2）磷酸化的影响。
在两种细胞系中均鉴定出功能性AT(2)受体以及Ang II，刺激这些受体可抑制EGF诱导的DNA合成和ERK2磷酸化。AT(1)受体虽然在两种细胞系中均有表达，但仅在LNCaP细胞中具有功能，其激活可刺激DNA合成。
功能性AT(2)受体存在，并且能够抑制LNCaP和快速生长的雄激素非依赖性PC3细胞系中EGF诱导的前列腺癌细胞生长，而功能性AT(1)受体仅在LNCaP细胞中发现，其激活可刺激DNA合成。
