Department of Veterinary Surgery and Anesthesiology, School of Veterinary Medicine and Animal Science, São Paulo State University-UNESP, Botucatu 18618-687, Brazil.
Department of Electrical Engineering, School of Electrical, Mechanical and Computer Engineering, Federal University of Goias-UFG, Goiania 74690-900, Brazil.
Int J Mol Sci. 2022 Jan 21;23(3):1163. doi: 10.3390/ijms23031163.
Canine prostate cancer (PC) is an aggressive disease, and dogs can be considered comparative models for human PC. In recent years, canine PC has been shown to resemble human castrate-resistant prostate cancer. The influx and efflux of testosterone in prostatic luminal cells are regulated by P-glycoprotein (P-gp). Therefore, human PC generally lacks P-gp expression and maintains the expression of androgen receptors (ARs). However, this co-expression has not previously been investigated in dogs. Therefore, this study aimed to evaluate AR and P-gp co-expression to elucidate these protein patterns in canine prostate samples. We identified AR/P-gp double immunofluorescence co-expression of both proteins in normal luminal cells. However, in canine PC, cells lack AR expression and exhibit increased P-gp expression. These results were confirmed by gene expression analyses. Overall, our results strongly suggest that normal canine prostate testosterone influx may be regulated by P-gp expression, and that during progression to PC, prostatic cells lack AR expression and P-gp overexpress. P-gp expression in canine PC may be related to a phenotype of multiple drug resistance.
犬前列腺癌（PC）是一种侵袭性疾病，犬可被视为人类 PC 的比较模型。近年来，犬前列腺癌已被证明类似于人类去势抵抗性前列腺癌。前列腺腔细胞中睾酮的内流和外流受 P-糖蛋白（P-gp）调节。因此，人类 PC 通常缺乏 P-gp 表达并维持雄激素受体（AR）的表达。然而，这种共表达以前并未在犬中进行过研究。因此，本研究旨在评估 AR 和 P-gp 的共表达，以阐明犬前列腺样本中的这些蛋白模式。我们在正常腔细胞中鉴定到了 AR/P-gp 双重免疫荧光共表达这两种蛋白。然而，在犬前列腺癌中，细胞缺乏 AR 表达，并表现出 P-gp 表达增加。这些结果通过基因表达分析得到了证实。总的来说，我们的研究结果强烈表明，正常犬前列腺中的睾酮内流可能受 P-gp 表达的调节，而在向 PC 进展过程中，前列腺细胞缺乏 AR 表达和 P-gp 过表达。犬前列腺癌中 P-gp 的表达可能与多药耐药表型有关。
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