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Lymphotoxin β receptor activation promotes bladder cancer in a nuclear factor-κB-dependent manner.

Shen M, Duan X, Zhou P, Zhou W, Wu X, Xu S, Chen Y, Tao Z - Mol Med Rep (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, P.R. China.

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.

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Related in: MedlinePlus

Immunohistochemical staining of (A) lymphotoxin β receptor (LTβR), (B) phosphorylated (p)-p65, and (C) p52 proteins in (A1–C1) healthy bladder mucosal and (A2–C2) chronic cystitis tissues. All three proteins are negatively stained in healthy bladder mucosa tissues and show strong positive staining in chronic cystitis tissues (×400).
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f1-mmr-11-02-0783: Immunohistochemical staining of (A) lymphotoxin β receptor (LTβR), (B) phosphorylated (p)-p65, and (C) p52 proteins in (A1–C1) healthy bladder mucosal and (A2–C2) chronic cystitis tissues. All three proteins are negatively stained in healthy bladder mucosa tissues and show strong positive staining in chronic cystitis tissues (×400).

Mentions: Weak to no LTβR protein expression was detected in healthy bladder mucosa, while positive staining was observed in the cytoplasm and nucleus of chronic cystitis and BCa tissues (Figs. 1 and 2). Positive staining of the LTβR protein (69.8%) in the BCa group was higher than that in healthy bladder mucosa one (13.3%), similarly to the cystitis (90.0%) group. The MD of the LTβR protein in the BCa group was significantly higher than that observed in the healthy group, as shown by a Student-Newman-Keuls test (P<0.05), similarly to the comparison between the chronic cystitis and the healthy group (P<0.05) (Table IV). The MD values of LTβR were significantly different between the histological grade, the clinical stage and the lymph node metastasis profile groups of BCa patients (all, P<0.05), while no significant association with age and gender (P>0.05) was observed (Table V and Fig. 2).


Lymphotoxin β receptor activation promotes bladder cancer in a nuclear factor-κB-dependent manner.

Shen M, Duan X, Zhou P, Zhou W, Wu X, Xu S, Chen Y, Tao Z - Mol Med Rep (2014)

Immunohistochemical staining of (A) lymphotoxin β receptor (LTβR), (B) phosphorylated (p)-p65, and (C) p52 proteins in (A1–C1) healthy bladder mucosal and (A2–C2) chronic cystitis tissues. All three proteins are negatively stained in healthy bladder mucosa tissues and show strong positive staining in chronic cystitis tissues (×400).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4262482&req=5

f1-mmr-11-02-0783: Immunohistochemical staining of (A) lymphotoxin β receptor (LTβR), (B) phosphorylated (p)-p65, and (C) p52 proteins in (A1–C1) healthy bladder mucosal and (A2–C2) chronic cystitis tissues. All three proteins are negatively stained in healthy bladder mucosa tissues and show strong positive staining in chronic cystitis tissues (×400).
Mentions: Weak to no LTβR protein expression was detected in healthy bladder mucosa, while positive staining was observed in the cytoplasm and nucleus of chronic cystitis and BCa tissues (Figs. 1 and 2). Positive staining of the LTβR protein (69.8%) in the BCa group was higher than that in healthy bladder mucosa one (13.3%), similarly to the cystitis (90.0%) group. The MD of the LTβR protein in the BCa group was significantly higher than that observed in the healthy group, as shown by a Student-Newman-Keuls test (P<0.05), similarly to the comparison between the chronic cystitis and the healthy group (P<0.05) (Table IV). The MD values of LTβR were significantly different between the histological grade, the clinical stage and the lymph node metastasis profile groups of BCa patients (all, P<0.05), while no significant association with age and gender (P>0.05) was observed (Table V and Fig. 2).

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Zhejiang 325000, P.R. China.

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.

Show MeSH
Related in: MedlinePlus