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      Dataset of HOXB7, HOXB8 and HOXB9 expression profiles in cell lines representative of the breast cancer molecular subtypes Luminal a (MCF7), Luminal b (BT474), HER2+ (SKBR3) and triple-negative (MDA231, MDA468), compared to a model of normal cells (MCF10A)

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          Abstract

          Alterations in HOXB genes expression in breast cancer have been described and related to therapy response and disease progression. However, due to breast cancer complexity and heterogeneity, added to the use of different technical approaches, the observed expression profiles are sometimes contradictory. Here, we provided the analyses of HOXB7, HOXB8 and HOXB9 expression profiles in cell lines extensively used in the literature addressing the putative role of HOXB genes in breast cancer (MCF7, BT474, SKBR3, MDA231 and MDA468) and representative of the clinical breast cancer molecular subtypes (Luminal A, Luminal B, HER2+ and Triple-negatives Claudin-low/Basal), compared to a normal breast model (MCF10A), using quantitative-PCR (qPCR). This technique allows a very sensitive quantification of gene expression and was performed using the fluorophore SYBR Green in order to obtain the expression levels relative to a reference gene, GAPDH in this case. We showed that HOXB7 is upregulated in all breast cancer cells analyzed, while HOXB8 and HOXB9 are significantly upregulated in MCF7 (Luminal A), BT474 (Luminal B) and MDA231 cells (Triple-negative Claudin-low). In addition, we found that the magnitude of the upregulation is highly subtype-specific, being the HER2+ cells the model with lowest HOXB7 upregulation, presenting very low or even null expression for HOXB8 and HOXB9, respectively. These results are analyzed in more detail in “HOX genes function in Breast Cancer development” [1] and are potentially relevant for a better understanding of the molecular heterogeneity of breast cancer, in addition to be a valuable tool assisting researchers in the choice of the most suitable cell models to perform functional assays concerning HOXB7, HOXB8 and HOXB9 genes.

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          HOXB7, a homeodomain protein, is overexpressed in breast cancer and confers epithelial-mesenchymal transition.

          Epithelial-mesenchymal transition (EMT) is increasingly recognized as a mechanism whereby cells in primary noninvasive tumors acquire properties essential for migration and invasion. Microarray analyses of microdissected epithelial cells from bone metastasis revealed a HOXB7 overexpression that was 3-fold higher than in primary breast carcinomas and 18-fold higher compared with normal breast. This led us to investigate the role of HOXB7 in neoplastic transformation of breast cells. Expression of HOXB7 in both MCF10A and Madin-Darby canine kidney (MDCK) epithelial cells resulted in the acquisition of both phenotypic and molecular attributes typical of EMT. Loss of epithelial proteins, claudin 1 and claudin 7, mislocalization of claudin 4 and E-cadherin, and the expression of mesenchymal proteins, vimentin and alpha-smooth muscle actin, were observed. MDCK cells expressing HOXB7 exhibited properties of migration and invasion. Unlike MDCK vector-transfected cells, MDCK-HOXB7 cells formed highly vascularized tumors in mice. MDCK-HOXB7 cells overexpressed basic fibroblast growth factor (bFGF), had more active forms of both Ras and RhoA proteins, and displayed higher levels of phosphorylation of p44 and p42 mitogen-activated protein kinase (MAPK; extracellular signal-regulated kinases 1 and 2). Effects initiated by HOXB7 were reversed by specific inhibitors of FGF receptor and the Ras-MAPK pathways. These data provide support for a function for HOXB7 in promoting tumor invasion through activation of Ras/Rho pathway by up-regulating bFGF, a known transcriptional target of HOXB7. Reversal of these effects by HOXB7-specific siRNA further suggested that these effects were mediated by HOXB7. Thus, HOXB7 overexpression caused EMT in epithelial cells, accompanied by acquisition of aggressive properties of tumorigenicity, migration, and invasion.
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            The HOXB7 protein renders breast cancer cells resistant to tamoxifen through activation of the EGFR pathway.

            Multiple factors including long-term treatment with tamoxifen are involved in the development of selective estrogen receptor (ER) modulator resistance in ERα-positive breast cancer. Many underlying molecular events that confer resistance are known but a unifying theme is yet to be revealed. In this report, we provide evidence that HOXB7 overexpression renders MCF-7 cells resistant to tamoxifen via cross-talk between receptor tyrosine kinases and ERα signaling. HOXB7 is an ERα-responsive gene. Extended treatment of MCF-7 cells with tamoxifen resulted in progressively increasing levels of HOXB7 expression, along with EGFR and EGFR ligands. Up-regulation of EGFR occurs through direct binding of HOXB7 to the EGFR promoter, enhancing transcriptional activity. Finally, higher expression levels of HOXB7 in the tumor significantly correlated with poorer disease-free survival in ERα-positive patients with breast cancer on adjuvant tamoxifen monotherapy. These studies suggest that HOXB7 acts as a key regulator, orchestrating a major group of target molecules in the oncogenic hierarchy. Functional antagonism of HOXB7 could circumvent tamoxifen resistance.
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              Analysis of HOX gene expression patterns in human breast cancer.

              HOX genes are highly conserved transcription factors that determine the identity of cells and tissues along the anterior-posterior body axis in developing embryos. Aberrations in HOX gene expression have been shown in various tumors. However, the correlation of HOX gene expression patterns with tumorigenesis and cancer progression has not been fully characterized. Here, to analyze putative candidate HOX genes involved in breast cancer tumorigenesis and progression, the expression patterns of 39 HOX genes were analyzed using breast cancer cell lines and patient-derived breast tissues. In vitro analysis revealed that HOXA and HOXB gene expression occurred in a subtype-specific manner in breast cancer cell lines, whereas most HOXC genes were strongly expressed in most cell lines. Among the 39 HOX genes analyzed, 25 were chosen for further analysis in malignant and non-malignant tissues. Fourteen genes, encoding HOXA6, A13, B2, B4, B5, B6, B7, B8, B9, C5, C9, C13, D1, and D8, out of 25 showed statistically significant differential expression patterns between non-malignant and malignant breast tissues and are putative candidates associated with the development and malignant progression of breast cancer. Our data provide a valuable resource for furthering our understanding of HOX gene expression in breast cancer and the possible involvement of HOX genes in tumor progression.
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                Author and article information

                Contributors
                Journal
                Data Brief
                Data Brief
                Data in Brief
                Elsevier
                2352-3409
                18 April 2020
                June 2020
                18 April 2020
                : 30
                : 105572
                Affiliations
                [a ]IBMC – Institute for Molecular and Cellular Biology, i3S – Institute for Innovation and Health Research, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal
                [b ]ICBAS – Institute of Biomedical Sciences Abel Salazar, University of Porto, Porto, Portugal
                Author notes
                [* ]Corresponding author at: IBMC – Institute for Molecular and Cellular Biology, i3S – Institute for Innovation and Health Research, University of Porto, Rua Alfredo Allen 208, 4200-135 Porto, Portugal. renata.freitas@ 123456ibmc.up.pt
                Article
                S2352-3409(20)30466-2 105572
                10.1016/j.dib.2020.105572
                7182708
                32346580
                a5850389-5c17-49d8-9c82-c0470d71946b
                © 2020 The Author(s)

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 23 March 2020
                : 6 April 2020
                : 7 April 2020
                Categories
                Biochemistry, Genetics and Molecular Biology

                hoxb genes,breast cancer,qpcr,cell lines,molecular classification

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