title: Lymphotoxin β receptor activation promotes bladder cancer in a nuclear factor-κB-dependent manner.
abstract: 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.
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, P.R. China.
authors.forename: Mo
authors.initials: M
authors.lastname: Shen
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, P.R. China.
authors.forename: Xiuzhi
authors.initials: X
authors.lastname: Duan
authors.affiliation: Wenzhou WuMa Community Health Service Center, Wenzhou 325000, P.R. China.
authors.forename: Ping
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, P.R. China.
authors.forename: Wu
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Pathology, The First Afﬁliated Hospital of Wenzhou Medical University, Zhejiang 325000, P.R. China.
authors.forename: Xiuling
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, P.R. China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Xu
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, P.R. China.
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Laboratory Medicine, The Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, P.R. China.
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Tao
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053259:Lymphotoxin beta Receptor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D016328:NF-kappa B / Q000378:metabolism*; D009367:Neoplasm Staging; D010766:Phosphorylation; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000235:genetics / Q000378:metabolism; D051841:Transcription Factor RelB / Q000235:genetics / Q000378:metabolism; D001743:Urinary Bladder / Q000378:metabolism / Q000473:pathology; D001749:Urinary Bladder Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D053259:Lymphotoxin beta Receptor; D016328:NF-kappa B; D012333:RNA, Messenger; D051996:Transcription Factor RelA; D051841:Transcription Factor RelB