NDLI: Loss of WIF-1 and Wnt5a expression is related to aggressiveness of sporadic breast cancer in Tunisian patients

Content Provider	Springer Nature Link
Author	Trifa, Fatma Karray Chouayekh, Sondes Jmal, Emna Jmaa, Zeineb Ben Khabir, Abdelmajid Sellami Boudawara, Tahia Frikha, Mounir Daoud, Jamel Mokdad Gargouri, Raja
Copyright Year	2013
Abstract	Activation of the Wnt/β-catenin signaling pathway is common in various human cancers. The aim of this study was to investigate the expression of 2 members of the Wnt family (WIF-1 and Wnt5a) in sporadic and hereditary breast cancer tissues. WIF-1, is a secreted antagonist that binds Wnt ligands, and therefore inhibits the canonical Wnt/β-catenin pathway. Wnt5a is one of the members of the noncanonical Wnt family that mainly acts through calcium signaling pathway. The expression of WIF-1 was analyzed by methylation-specific PCR and RT-PCR, and the level of Wnt5a ligand was quantified by RT-QPCR in breast cancer tissues. Methylation of WIF-1 was detected in 71.3 % and 81.8 % of sporadic and hereditary cases, respectively. Aberrant methylation of WIF-1 was associated with advanced TNM stage and triple negative cases in sporadic breast carcinoma (p = 0.001 and p = 0.037, respectively). In hereditary cases, methylation of WIF-1 correlated with age at diagnosis (p = 0.027) and p53 status (p = 0.035). Regarding patients’ survival, WIF-1 methylated promoter conferred a reduced overall survival rate, and particularly in a group of patients with advanced TNM stage (p log rank = 0.006). Furthermore, aberrant CpG methylation of the WIF-1 promoter was significantly associated with transcriptional silencing of this tumor suppressor gene in sporadic breast cancer tissues (p = 0.036). On the other hand, in sporadic tumor tissues, the level of Wnt5a mRNA was significantly lower compared to normal tissues (p = 0.031) and lower still in those showing more aggressive behavior, suggesting that Wnt5a, a ligand involved in the noncanonical Wnt/β-catenin pathway, could act as a tumor suppressor gene in breast cancer.
Starting Page	1625
Ending Page	1633
Page Count	9
File Format	PDF
ISSN	10104283
Journal	Tumor Biology
Volume Number	34
Issue Number	3
e-ISSN	14230380
Language	English
Publisher	Springer Netherlands
Publisher Date	2013-02-16
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Breast cancer WIF-1 Methylation Transcriptional silencing Wnt5a Tumor suppressor Cancer Research
Content Type	Text
Resource Type	Article
Subject	Medicine Cancer Research

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