Home FOR AUTHORS Neoplasma 2012 Neoplasma Vol.59, No.2, p.216-223, 2012

Journal info


6 times a year.
Founded: 1954
ISSN 0028-2685
ISSN 1338-4317 (online)

Published in English

Editorial Info
Abstracted and Indexed
Submission Guidelines

Select Journal







Webshop Cart

Your Cart is currently empty.
Info: Your browser does not accept cookies. To put products into your cart and purchase them you need to enable cookies.

Neoplasma Vol.59, No.2, p.216-223, 2012

Title: Cigarette smoking extract causes hypermethylation and inactivation of WWOX gene in T-24 human bladder cancer cells
Author: W. YANG, S. CUI, J. MA, Q. LU, C. KONG, T. LIU, Z. SUN
Abstract: Genomic, epigenetic and expression alterations of WW domain containing oxidoreductase (WWOX) have been implicated in multiple tumor types. The current study was designed to examine the expression of WWOX in tumor tissues of human bladder transitional cell carcinoma (BTCC) and the influence of cigarette smoke extract (CSE) on WWOX expression and methylation status in T-24 bladder cancer cells. WWOX protein expression was evaluated by immunohistochemistry staining in a series of tumor samples from 78 patients with BTCC and 26 normal bladder tissues. The expression level and methylation status of WWOX in CSE-treated cells were examined by using quantitative Real-Time RT-PCR and methylation specific PCR, respectively. The expression levels of DNA methyltransferases (DNMTs) 1, 3A and 3B were also detected. We found that WWOX expression was absent or reduced in 79.5% (62/78) of BTCC tissues, but only in 19.2% (5/26) of normal bladder tissues. Loss of WWOX expression was correlated with tumor grade (P=0.019) and cigarette smoking (P=0.031), but was not associated with age, gender, tumor size and tumor number. Hypermethylation of WWOX promoter and exon 1 was specifically induced by CSE with a kinetics concurrent to the suppression of WWOX mRNA in T-24 cells. Furthermore, CSE treatment induced a significant time-dependent increase in the level of DNMT1, but has no effects on DNMT3A and DNMT3B. Taken together, these novel findings suggest that hypermethylation of WWOX induced by cigarette smoking may represent one underlying mechanism for the loss expression of WWOX in bladder cancer.
Keywords: WWOX, bladder cancer, immunohistochemistry, cigarette smoking, DNA methylation
Received: 19-Sep-2011 Published online: 24-Nov-2011
Year: 2012, Volume: 59, Issue: 2 Page From: 216, Page To: 223
doi:10.4149/neo_2012_028


download file


© AEPress s.r.o
Copyright notice: For any permission to reproduce, archive or otherwise use the documents in the ELiS, please contact AEP.