Laboratory of Biochemical and Molecular Pharmacology, Universidade Federal do Rio de Janeiro, Brazil.
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Mexico.
Life Sci. 2019 Dec 15;239:117048. doi: 10.1016/j.lfs.2019.117048. Epub 2019 Nov 12.
Benign prostatic hyperplasia (BPH) is an aging-related and progressive disease linked to an up-regulation of α-adrenoceptors. The participation of EGF receptors (EGFR) in the GPCRs' signalosome has been described but so far data about the contribution of these receptors to prostatic stromal hyperplasia are scanty. We isolated and cultured vimentin-positive prostate stromal cells obtained from BPH patients. According to intracellular Ca measurements, cell proliferation and Western blotting assays, these cultured hyperplastic stromal cells express functional αadrenoceptors and EGFR, and proliferate in response to the αadrenoceptor agonist phenylephrine. Interestingly, in these cells the inhibition of EGFR signaling with GM6001, CRM197, AG1478 or PD98059 was associated with full blockage of α-adrenoceptor-mediated cell proliferation, while cell treatment with each inhibitor alone did not alter basal cell growth. Moreover, the co-incubation of AG1478 (EGFR inhibitor) with αα-adrenoceptor antagonists showed no additive inhibitory effect. These findings highlight a putative role of EGFR signaling to α-adrenoceptor-mediated human prostate hyperplasia, suggesting that the inhibition of this transactivation cascade could be useful to reduce BPH progression.
良性前列腺增生（BPH）是一种与 α-肾上腺素能受体上调有关的与年龄相关的进行性疾病。已经描述了表皮生长因子受体（EGFR）在 GPCRs 信号小体中的参与，但迄今为止，关于这些受体对前列腺基质增生的贡献的数据很少。我们从 BPH 患者中分离并培养了波形蛋白阳性的前列腺基质细胞。根据细胞内 Ca 测量、细胞增殖和 Western blot 分析，这些培养的增生性基质细胞表达功能性 α-肾上腺素能受体和 EGFR，并对 α-肾上腺素能受体激动剂苯肾上腺素产生增殖反应。有趣的是，在这些细胞中，用 GM6001、CRM197、AG1478 或 PD98059 抑制 EGFR 信号通路与完全阻断 α-肾上腺素能受体介导的细胞增殖相关，而单独用每种抑制剂处理细胞不会改变基础细胞生长。此外，AG1478（EGFR 抑制剂）与 αα-肾上腺素能受体拮抗剂的共孵育没有显示出相加的抑制作用。这些发现强调了 EGFR 信号在 α-肾上腺素能受体介导的人类前列腺增生中的潜在作用，表明抑制这种转导级联可能有助于减少 BPH 的进展。
