Rubenwolf Peter C, Otto Wolfgang, Denzinger Stefan, Hofstädter Ferdinand, Wieland Wolf, Georgopoulos Nikolaos T
World J Urol. 2014 Aug;32(4):991-7. doi: 10.1007/s00345-013-1153-9.
To study the expression, localization and potential clinical significance of aquaporin water channels both in well-established urothelial cancer (UC) cell lines and in human bladder carcinoma specimens of different stages and grades and to discuss the clinical relevance of the findings.
AQP transcript and protein expression by RT4, RT112 and T24 UC cell lines was investigated using reverse transcriptase polymerase chain reaction and immunofluorescence labelling. Immunohistochemistry (IHC) was used to assess AQP protein expression in 94 UC specimens of various grades and stages.
AQP3 and 9 transcripts were expressed in low-grade RT4 and RT112, but not in high-grade T24 cells. By contrast, AQP4 mRNA was absent in RT4, but expressed by RT112 and T24. Transcripts for AQP7 and 11 were detected in all three UC cell lines. Immunofluorescence microscopy confirmed the expression of AQP3, 4 and 7 at the protein level. By IHC, AQP3 was shown to be intensely expressed by 86 %, 66 % and 33 % of specimens of stage pTa, pT1 and pT2 tumours, respectively (p < 0.001). Whereas 100 % of G1 tumours were positive, only 73 % and 55 % of G2 and G3 tumours were found to express AQP3 (p = 0.004).
This is the first study to demonstrate that several AQPs are expressed in UC. Our results indicate that there is a correlation between AQP3 protein expression and tumour stage and grade, with AQP3 expression being reduced or lost in tumours of higher grade and stage. Taken together with the available evidence from other studies, we conclude that AQPs may play a role in the progression of UC and, in particular, that this could be of prognostic value.
研究水通道蛋白水通道在成熟的尿路上皮癌（UC）细胞系以及不同分期和分级的人膀胱癌标本中的表达、定位及潜在临床意义，并探讨研究结果的临床相关性。
采用逆转录聚合酶链反应和免疫荧光标记法，研究RT4、RT112和T24 UC细胞系中AQP转录本和蛋白表达情况。免疫组织化学（IHC）用于评估94例不同分级和分期的UC标本中AQP蛋白表达。
AQP3和9转录本在低级别RT4和RT112中表达，但在高级别T24细胞中不表达。相比之下，RT4中不存在AQP4 mRNA，但RT112和T24表达。在所有三种UC细胞系中均检测到AQP7和11的转录本。免疫荧光显微镜证实了AQP3、4和7在蛋白水平的表达。通过IHC显示，pTa、pT1和pT2期肿瘤标本中分别有86%、66%和33%强烈表达AQP3（p<0.001）。G1肿瘤100%呈阳性，而G2和G3肿瘤中分别只有73%和55%表达AQP3（p = 0.004）。
这是第一项证明多种水通道蛋白在UC中表达的研究。我们的结果表明，AQP3蛋白表达与肿瘤分期和分级之间存在相关性，在更高分级和分期的肿瘤中AQP3表达降低或缺失。结合其他研究的现有证据，我们得出结论，水通道蛋白可能在UC进展中起作用，特别是这可能具有预后价值。
