Shen Mo, Duan Xiuzhi, Zhou Ping, Zhou Wu, Wu Xiuling, Xu Siqi, Chen Yuhua, Tao Zhihua
Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, P.R. China.
Department of Laboratory Medicine, The Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, P.R. China.
Mol Med Rep. 2015 Feb;11(2):783-90. doi: 10.3892/mmr.2014.2826. Epub 2014 Oct 30.
Bladder cancer (BCa) is the most common tumor of the urinary system. Chronic inflammation in the papillary urothelial neoplasm of low malignant potential (PUNLMP)may contribute to carcinogenesis, including that of BCa, via poorly understood mechanisms. In this study, we show that the lymphotoxin β receptor (LTβR) is upregulated in BCa via activation of the canonical and non-canonical nuclear factor-κB (NF-κB) pathways. The mRNA expression of LTβR in 81 BCa, 10 chronic cystitis and 23 healthy bladder mucosa tissues was investigated by reverse transcription-fluorescent quantitative polymerase chain reaction (RT-FQ-PCR), and protein expression was studied in 73 BCa, 30 cystitis and 15 healthy paraffin-embedded tissue sections by immunohistochemistry. Both LTβR mRNA and protein were upregulated in BCa and cystitis compared to the healthy group (P<0.05). The mRNA level of the downstream NF-κB canonical pathway p65 gene and of the non-canonical pathway RelB gene were higher in the BCa and cystitis groups compared to the healthy one. The level of phosphorylated p65 (p-p65) protein of the canonical NF-κB pathway and that of p52, a protein of the non-canonical NF-κB pathway, were also higher in the BCa and cystitis group compared to the healthy group. The levels of these proteins significantly correlated to the pathological grade, clinical stage and lymph node metastasis of BCa patients (P<0.05). In addition, there was a positive correlation between LTβR and NF-κB pathway proteins. Thus, LTβR signaling may be involved in promoting BCa through the NF-κB pathway, and which may represent the molecular link between inflammation and BCa.
膀胱癌（BCa）是泌尿系统最常见的肿瘤。低恶性潜能乳头状尿路上皮肿瘤（PUNLMP）中的慢性炎症可能通过尚不清楚的机制促进包括BCa在内的肿瘤发生。在本研究中，我们发现淋巴毒素β受体（LTβR）在BCa中通过经典和非经典核因子κB（NF-κB）途径的激活而上调。通过逆转录荧光定量聚合酶链反应（RT-FQ-PCR）研究了81例BCa、10例慢性膀胱炎和23例健康膀胱黏膜组织中LTβR的mRNA表达，并通过免疫组织化学研究了73例BCa、30例膀胱炎和15例健康石蜡包埋组织切片中的蛋白表达。与健康组相比，BCa和膀胱炎中LTβR的mRNA和蛋白均上调（P<0.05）。与健康组相比，BCa和膀胱炎组中NF-κB经典途径p65基因和非经典途径RelB基因的mRNA水平更高。经典NF-κB途径的磷酸化p65（p-p65）蛋白水平和非经典NF-κB途径的蛋白p52水平在BCa和膀胱炎组中也高于健康组。这些蛋白水平与BCa患者的病理分级、临床分期和淋巴结转移显著相关（P<0.05）。此外LTβR与NF-κB途径蛋白之间存在正相关。因此，LTβR信号可能通过NF-κB途径参与促进BCa，这可能代表炎症与BCa之间的分子联系。
