Endocrinology Division, Department of Medicine, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Prostate. 2013 Jul;73(10):1057-68. doi: 10.1002/pros.22653. Epub 2013 Feb 6.
Evidence shows that angiotensin II type 1 receptor (AT1R) blockers may be associated with improved outcome in prostate cancer patients. It has been proposed that part of this effect could be due to angiotensin II type 2 receptor (AT2R) activation, the only active angiotensin II receptor in this situation. This study aimed to characterize the localization and expression of AT2R in prostate tissues and to assess its role on cell morphology and number in prostatic epithelial cells in primary culture.
AT2R and its AT2R-interacting protein (ATIP) expression were assessed on non-tumoral and tumoral human prostate using tissue microarray immunohistochemistry, binding assay, and Western blotting. AT2R effect on cell number was measured in primary cultures of epithelial cells from non-tumoral human prostate.
AT2R was localized at the level of the acinar epithelial layer and its expression decreased in cancers with a Gleason score 6 or higher. In contrast, ATIP expression increased with cancer progression. Treatment of primary cell cultures from non-tumoral prostate tissues with C21/M024, a selective AT2R agonist, alone or in co-incubation with losartan, an AT1R antagonist, significantly decreased cell number compared to untreated cells.
AT2R and ATIP are present in non-tumoral human prostate tissues and differentially regulated according to Gleason score. The decrease in non-tumoral prostate cell number upon selective AT2R stimulation suggests that AT2R may have a protective role against prostate cancer development. Treatment with a selective AT2R agonist could represent a new approach for prostate cancer prevention or for patients on active surveillance.
有证据表明，血管紧张素 II 型 1 型受体（AT1R）阻滞剂可能与前列腺癌患者的预后改善有关。有人提出，这种作用的部分原因可能是由于血管紧张素 II 型 2 型受体（AT2R）的激活，这是这种情况下唯一活跃的血管紧张素 II 受体。本研究旨在描述 AT2R 在前列腺组织中的定位和表达，并评估其在原代培养的前列腺上皮细胞中对细胞形态和数量的作用。
使用组织微阵列免疫组织化学、结合测定和 Western blot 评估非肿瘤和肿瘤人前列腺中的 AT2R 及其 AT2R 相互作用蛋白（ATIP）表达。在非肿瘤人前列腺的上皮细胞原代培养物中测量 AT2R 对细胞数量的影响。
AT2R 定位于腺上皮层水平，其表达在 Gleason 评分 6 或更高的癌症中降低。相比之下，ATIP 的表达随着癌症的进展而增加。用选择性 AT2R 激动剂 C21/M024 单独或与 AT1R 拮抗剂洛沙坦共同孵育处理非肿瘤前列腺组织的原代细胞培养物，与未处理的细胞相比，细胞数量明显减少。
AT2R 和 ATIP 存在于非肿瘤人前列腺组织中，并根据 Gleason 评分差异调节。选择性 AT2R 刺激后非肿瘤前列腺细胞数量减少表明 AT2R 可能对前列腺癌的发展具有保护作用。用选择性 AT2R 激动剂治疗可能代表预防前列腺癌或对主动监测患者的新方法。
