Expression and regulation of tumor suppressor gene maspin in human bladder cancer.
Maspin is a member of serine protease inhibitor family with tumor suppressing activity for breast and prostate cancers, acting at the level of tumor invasion and metastasis. However, there have been no published data regarding the role of maspin in human bladder cancer. We evaluated maspin expression in 65 series of bladder cancer samples (22 transurethral resection (TUR) and 43 radical cystectomy) and studied the regulatory mechanism of maspin gene activation in bladder cancer cells. Maspin expression was immunohistochemically detected in four (18.2%) patients with TUR and 22 (51.2%) patients with radical cystectomy whereas no expression was observed in normal transitional cells located at tumor-free area in bladder. The maspin expression was significantly correlated with the development of muscle invasive bladder cancer (P=0.00008). Using a luciferase reporter system, maspin promoter activity was induced in the maspin-positive bladder cancer cell lines as well as maspin-negative RT4 cells. Furthermore, treatment with the DNA methyltransferase inhibitor, 5-aza-2' deoxycytidine, and histone deacetylase inhibitor, trichostatin A, led to re-expression of maspin in RT4 cells. Our results indicate that maspin may contribute to bladder cancer development and that DNA methylation and histone deacetylation may be important for regulating maspin gene activation in bladder cancer cells.
Sugimoto
Shuji
S
Department of Urology, University of Kiel, Arnold-Heller-strasse 7, Kiel 24105, Germany.
Maass
Nicolai
N
Takimoto
Yukie
Y
Sato
Katsuhiko
K
Minei
Sadatsugu
S
Zhang
Ming
M
Hoshikawa
Yutaka
Y
Jünemann
Klaus-Peter
KP
Jonat
Walter
W
Nagasaki
Koichi
K
D000328:Adult; D000368:Aged; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002295:Carcinoma, Transitional Cell / Q000378:metabolism; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D019175:DNA Methylation; D000077209:Decitabine; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D017930:Genes, Reporter; D016147:Genes, Tumor Suppressor; D006657:Histones / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000494:pharmacology; D007150:Immunohistochemistry; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000096:biosynthesis* / Q000235:genetics*; D015533:Transcriptional Activation; D001749:Urinary Bladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D006657:Histones; D006877:Hydroxamic Acids; D011506:Proteins; C085344:SERPIN-B5; D015843:Serpins; C012589:trichostatin A; D000077209:Decitabine; D008156:Luciferases; D001374:Azacitidine