Overexpression of annexin a1 induced by terephthalic acid calculi in rat bladder cancer

Abstract

Prolonged cell proliferation in response to irritation by bladder calculi can evoke malignant transformation of the urothelium. However, the molecular mechanisms responsible for calculi-associated bladder carcinogenesis are unknown. We compared the protein expression pattern of rat bladder transitional cell carcinomas (TCCs) induced by terephthalic acid with that of normal bladder tissues using 2-DE. Comparative analysis of the respective spot patterns on 2-DE showed 146 spots that were markedly changed in TCC samples. Subsequently, 56 of the variant protein spots were identified by MALDI-TOF MS. Among them, overexpression of annexin a1 (ANNA1) in rat TCCs was confirmed by Western blotting and real-time RT-PCR analysis. Immunohistochemical staining revealed that ANNA1, usually a cytoplasmic protein in normal urothelium, was translocated to the nucleus in rat bladder cancer cells. In contrast to the animal studies, examination of human clinical specimens showed that ANNA1 expression was reduced in TCC compared to normal urothelium. The expression of ANNA1 was inversely related to the level of differentiation of TCC. Our data suggest that overexpression of ANNA1 is involved in bladder carcinogenesis induced by bladder calculi and that translocation of the protein may be partly responsible for the effect. ANNA1 may serve as a new marker of differentiation for the histopathological grading of human TCC.

Annexin A1 in Malignant Tumors: Current Opinions and Controversies

“…Annexin A1 may have important regulatory roles in tumor development and progression, but these findings are highly controversial, and the mechanism of its involvement in carcinogenesis and tumor progression is unclear. The downregulation of annexin A1 expression in certain cancers (8–28) and the upregulation in other cancer types support this involvement (19, 28–45). Table I summarizes the studies performed on clinical cancer cells and tissues with decreased annexin A1 expression.…”

Annexin A1 in Malignant Tumors: Current Opinions and Controversies

“…Annexin A1 may have important regulatory roles in tumor development and progression, but these findings are highly controversial, and the mechanism of its involvement in carcinogenesis and tumor progression is unclear. The downregulation of annexin A1 expression in certain cancers (8–28) and the upregulation in other cancer types support this involvement (19, 28–45). Table I summarizes the studies performed on clinical cancer cells and tissues with decreased annexin A1 expression.…”

Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO

“…Current studies on ANXA1 in BLCA were divergent. According to the study of Cui et al., ANXA1 was downregulated in murine-derived bladder cell carcinoma [ 34 ]. However, some studies demonstrated that ANXA1 was upregulated in BLCA and promoted BLCA progression [ 35 , 36 ].…”

The Expression Pattern of Annexin A1 in Urinary Bladder Urothelial Carcinoma and Its Clinicopathologic Significance

“…There are two contradictory results on the expression of AN-XA1 in UC. Cui et al 23 demonstrated that ANXA1 expression was inversely related to the level of differentiation of UC in all subcellular location, however, their UC sample size was limited to 26 cases and there was no description of ANXA1 expression in CIS. On the contrary, Li et al 24 reported ANXA1 up-regulation in higher pT status and histologic grade of UC, suggesting that ANXA1 might be related to tumor progression.…”

Annexin A1 in Malignant Tumors: Current Opinions and Controversies

“…Annexin A1 may have important regulatory roles in tumor development and progression, but these findings are highly controversial, and the mechanism of its involvement in carcinogenesis and tumor progression is unclear. The downregulation of annexin A1 expression in certain cancers (8–28) and the upregulation in other cancer types support this involvement (19, 28–45). Table I summarizes the studies performed on clinical cancer cells and tissues with decreased annexin A1 expression.…”

Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO

“…Current studies on ANXA1 in BLCA were divergent. According to the study of Cui et al., ANXA1 was downregulated in murine-derived bladder cell carcinoma [ 34 ]. However, some studies demonstrated that ANXA1 was upregulated in BLCA and promoted BLCA progression [ 35 , 36 ].…”

The Expression Pattern of Annexin A1 in Urinary Bladder Urothelial Carcinoma and Its Clinicopathologic Significance

“…There are two contradictory results on the expression of AN-XA1 in UC. Cui et al 23 demonstrated that ANXA1 expression was inversely related to the level of differentiation of UC in all subcellular location, however, their UC sample size was limited to 26 cases and there was no description of ANXA1 expression in CIS. On the contrary, Li et al 24 reported ANXA1 up-regulation in higher pT status and histologic grade of UC, suggesting that ANXA1 might be related to tumor progression.…”

Annexin A1 in Malignant Tumors: Current Opinions and Controversies

“…Annexin A1 may have important regulatory roles in tumor development and progression, but these findings are highly controversial, and the mechanism of its involvement in carcinogenesis and tumor progression is unclear. The downregulation of annexin A1 expression in certain cancers (8–28) and the upregulation in other cancer types support this involvement (19, 28–45). Table I summarizes the studies performed on clinical cancer cells and tissues with decreased annexin A1 expression.…”

Peptidase inhibitor (PI16) impairs bladder cancer metastasis by inhibiting NF-κB activation via disrupting multiple-site ubiquitination of NEMO

“…Current studies on ANXA1 in BLCA were divergent. According to the study of Cui et al., ANXA1 was downregulated in murine-derived bladder cell carcinoma [ 34 ]. However, some studies demonstrated that ANXA1 was upregulated in BLCA and promoted BLCA progression [ 35 , 36 ].…”

The Expression Pattern of Annexin A1 in Urinary Bladder Urothelial Carcinoma and Its Clinicopathologic Significance

“…There are two contradictory results on the expression of AN-XA1 in UC. Cui et al 23 demonstrated that ANXA1 expression was inversely related to the level of differentiation of UC in all subcellular location, however, their UC sample size was limited to 26 cases and there was no description of ANXA1 expression in CIS. On the contrary, Li et al 24 reported ANXA1 up-regulation in higher pT status and histologic grade of UC, suggesting that ANXA1 might be related to tumor progression.…”