Background: In normal prostate cells, receptors for oxytocin (OT), a peptide involved in regulating prostate growth are sequestered within membrane microdomains called caveolae. During cancer progression, polymerase-transcript-release factor (PTRF) is downregulated, caveolae structures are lost and receptors move onto the cell membrane. This study investigated whether proteins responsible for caveolae formation were affected by the OT peptide, also, how OT treatment affected oxytocin receptor (OTR) movement within living cells. Methods: Normal human prostate epithelial cells (PrEC) expressing caveolin and PTRF and androgen-independent (PC3) cancer cells expressing caveolin but not PTRF were used. OTR, caveolin and PTRF expression was determined in human prostate tissue. Results: PTRF expression decreased in tissue alongside an increase in malignancy. Caveolin-1 expression was downregulated by OT treatment. Caveolin-2 was decreased by OT in PrEC cells but increased in PC3 cells. PTRF was decreased by OT in PrEC. TIRF microscopy showed OTR translocated from caveolae to caveolae in normal cells, whereas OTR moved without restraint in malignant cells, possibly stimulating signaling pathways. Conclusions: This study provides evidence for the ability of OT to regulate caveolin and PTRF expression. This study elucidates possible mechanisms by which cell receptors and caveolae proteins interact to enhance cell proliferation.
背景：在正常前列腺细胞中，参与调节前列腺生长的肽类激素催产素（OT）的受体被隔离在称为小窝的膜微域内。在癌症进展过程中，聚合酶转录释放因子（PTRF）表达下调，小窝结构消失，受体转移到细胞膜上。本研究探讨了负责小窝形成的蛋白质是否受OT肽影响，以及OT处理如何影响活细胞内催产素受体（OTR）的移动。方法：使用表达小窝蛋白和PTRF的正常人前列腺上皮细胞（PrEC），以及表达小窝蛋白但不表达PTRF的雄激素非依赖性（PC3）癌细胞。检测了人前列腺组织中OTR、小窝蛋白和PTRF的表达。结果：组织中PTRF表达随恶性程度增加而降低。OT处理下调了小窝蛋白-1的表达。在PrEC细胞中OT降低了小窝蛋白-2的表达，而在PC3细胞中则增加。OT降低了PrEC细胞中PTRF的表达。全内反射荧光显微镜显示，在正常细胞中OTR从小窝间迁移，而在恶性细胞中OTR则不受限制地移动，可能刺激信号通路。结论：本研究为OT调节小窝蛋白和PTRF表达的能力提供了证据，阐明了细胞受体与小窝蛋白相互作用促进细胞增殖的可能机制。
Location and Movement of the Oxytocin Receptor Differ Between the Normal and Diseased Prostate
肿瘤(癌症)患者之家