Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression

• Published in: Experimental and molecular pathology 2015-12, Vol.99 (3), p.409-415
• Main Authors: Nascimento, Jessica Catarine Frutuoso do, Ferreira, Steffany de Almeida, Vasconcelos, Juliana Lúcia de Albuquerque, Silva-Filho, João Luiz Quirino da, Barbosa, Bruno Trajano, Bezerra, Matheus Filgueira, Rocha, Cíntia Renata Costa, Beltrão, Eduardo Isidoro Carneiro
• Format: Article
• Language: English
• Subjects: Brazil; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Carcinoma, Ductal, Breast - genetics; Carcinoma, Ductal, Breast - pathology; Female; Fucosyltransferases - genetics; Fucosyltransferases - metabolism; FucT-III; Gene Expression Regulation, Neoplastic - genetics; Human mammary carcinoma; Humans; Immunohistochemistry - methods; Lewis X Antigen - metabolism; Promoter Regions, Genetic; Protein expression; Regulatory region; Single nucleotide polymorphism
• ISSN: 0014-4800; 1096-0945
• DOI: 10.1016/j.yexmp.2015.08.015

Fucosylated glycans synthesized by α1,3/4-fucosyltransferase (FUT3) enzyme play an important role in breast cancer prognosis and metastasis, being involved in the binding of circulating tumor cells to the endothelium and being related to tumor stage, metastatic potential and chemoresistance. Despite the pro-tumor action of this enzyme, studies have demonstrated its role in natural killer-induced cytotoxicity through the recognition of sialyl Lewis X by C-type lectin receptors and through extrinsic apoptosis pathway triggered by Apo2L-TRAIL. This study aimed to investigate the expression pattern of FUT3 in invasive breast carcinoma (IDC) from patients of Pernambuco state, Northeast of Brazil, and genotype FUT3 promoter region to identify possible SNPs that could be associated with variations in FUT3 expression. Immunohistochemistry assay was used to access the FUT3 expression in normal (n=11) and tumor tissues (n=85). DNA sequencing was performed to genotype the FUT3 promoter region in patients with IDC (n=109) and healthy controls (n=110). Our results demonstrated that the absence of FUT3 enzyme is related to breast's IDC. The non-expression of FUT3 was more frequent in larger lesions and also in HER2 negative IDC tumors. Genomic analysis showed that two variations localized in FUT3 promoter region are possibly associated with IDC. Our results suggest that minor allele T of SNP rs73920070 (−6933 C>T) confers protection whereas minor allele T of SNP rs2306969 (−6951 C>T) triggers to susceptibility to IDC in the population of Pernambuco state, Northeast of Brazil. •Lack of FUT3 expression in breast tissues was related to invasive ductal carcinoma.•Lack of FUT3 expression was more frequent in larger tumors and HER-2 (−) samples.•Allele T of FUT3 SNP rs73920070 was more frequent in cancer-free individuals.•Allele T of FUT3 SNP rs2306969 was more frequent in IDC patients.•In our model, FUT3 absence in breast IDC samples is an immune resistance mechanism.