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

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Tumor Biology

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.

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Acknowledgments

This work was supported by a grant of the Tunisian Ministry of High Education and Scientific Research. We thank technicians at CHU Habib Bourguiba at Sfax—Tunisia for assistance.

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We guarantee that there are no financial and personal relationships with other people or organizations that might pose a conflict of interest in connection with this work.

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Authors and Affiliations

  1. Laboratory of Biomass Valorisation and Production of Eukaryotic Proteins, Center of Biotechnology of Sfax, University of Sfax, Sidi Mansour street, BP“K”1177, Sfax, 3018, Tunisia

    Fatma Trifa, Sondes Karray-Chouayekh, Emna Jmal, Zeineb Ben Jmaa & Raja Mokdad-Gargouri

  2. Centre Hospitalo-Universitaire Habib Bourguiba Sfax, Sfax, 3000, Tunisia

    Abdelmajid Khabir, Tahia Sellami-Boudawara, Mounir Frikha & Jamel Daoud

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  1. Fatma Trifa
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Correspondence to Raja Mokdad-Gargouri.

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Trifa, F., Karray-Chouayekh, S., Jmal, E. et al. Loss of WIF-1 and Wnt5a expression is related to aggressiveness of sporadic breast cancer in Tunisian patients. Tumor Biol. 34, 1625–1633 (2013). https://doi.org/10.1007/s13277-013-0694-2

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  • DOI: https://doi.org/10.1007/s13277-013-0694-2

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