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

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...

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Veröffentlicht in:Experimental and molecular pathology 2015-12, Vol.99 (3), p.409-415
Hauptverfasser: 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
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container_end_page 415
container_issue 3
container_start_page 409
container_title Experimental and molecular pathology
container_volume 99
creator 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
description 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.
doi_str_mv 10.1016/j.yexmp.2015.08.015
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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. 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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. 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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&gt;T) confers protection whereas minor allele T of SNP rs2306969 (−6951 C&gt;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.</abstract><cop>Netherlands</cop><pub>Elsevier Inc</pub><pmid>26321244</pmid><doi>10.1016/j.yexmp.2015.08.015</doi><tpages>7</tpages></addata></record>
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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
title Fut3 role in breast invasive ductal carcinoma: Investigating its gene promoter and protein expression
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