Overexpression of annexin a1 induced by terephthalic acid calculi in rat bladder cancer.
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.
Cui
Lunbiao
L
Key Laboratory of Reproductive Medicine, Institute of Toxicology, Nanjing Medical University, Nanjing, China.
Wang
Yubang
Y
Shi
Yuan
Y
Zhang
Zhengdong
Z
Xia
Yankai
Y
Sun
Hong
H
Wang
Shouling
S
Chen
Jianfeng
J
Zhang
Wei
W
Lu
Qiang
Q
Song
Ling
L
Wei
Qingyi
Q
Zhang
Ruiwen
R
Wang
Xinru
X
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D017305:Annexin A1 / Q000096:biosynthesis / Q000737:chemistry / Q000235:genetics*; D015153:Blotting, Western; D002295:Carcinoma, Transitional Cell / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D002467:Cell Nucleus / Q000378:metabolism; D004195:Disease Models, Animal; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D010795:Phthalic Acids; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D001744:Urinary Bladder Calculi / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism; D001749:Urinary Bladder Neoplasms / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism
D017305:Annexin A1; D010795:Phthalic Acids; C011363:terephthalic acid