title: IL-1β induces up-regulation of BIRC3, a gene involved in chemoresistance to doxorubicin in breast cancer cells.
abstract: Epithelial to mesenchymal transition (EMT) of tumor cells facilitates their progress to metastasis. In the tumor microenvironment the inflammatory cytokine 1β (IL-1β) has been associated with tumor development and invasiveness. IL-1β-induced EMT triggers the expression of markers associated with malignancy. We have recently reported that an IL-1β-highly responsive clone (6D cells) from non-invasive MCF-7 breast cancer cells activates PI3K/Rac and IL-1RI/β-catenin pathways that up-regulate the transcription of genes involved in an EMT-like process. However, a correlation between the EMT program induced by a pro-inflammatory environment, and the acquisition of chemoresistance has not been yet determined in these cells. In this work, we report the expression of cell survival genes after IL-1β stimulation of 6D cells. The expression of CDKN1A, TP63, SFN and, particularly, BIRC3 was found to be up-regulated in a RNA-seq analysis and validated by qPCR. Cells stimulated with IL-1β when challenged with doxorubicin showed resistance to the drug, whereas silencing of BIRC3 decreased viability of the cells treated with the drug. Our present results show that IL-1β confers doxorubicin resistance to breast cancer cells, underlining the importance of an inflammatory environment in cancer malignancy.
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Ciudad de México 07360, Mexico.
authors.forename: Mónica
authors.initials: M
authors.lastname: Mendoza-Rodríguez
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Ciudad de México 07360, Mexico; Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Colonia Doctores, Ciudad de México 06720, Mexico.
authors.forename: Haruki
authors.initials: H
authors.lastname: Arévalo Romero
authors.affiliation: Unidad de Investigación en Virología y Cáncer, Hospital Infantil de México Federico Gómez, Dr. Márquez 162, Colonia Doctores, Ciudad de México 06720, Mexico.
authors.forename: Ezequiel M
authors.initials: EM
authors.lastname: Fuentes-Pananá
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Ciudad de México 07360, Mexico.
authors.forename: Jorge-Tonatiuh
authors.initials: JT
authors.lastname: Ayala-Sumuano
authors.affiliation: Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Avenida Instituto Politécnico Nacional 2508, San Pedro Zacatenco, Ciudad de México 07360, Mexico. Electronic address: imeza@cinvestav.mx.
authors.forename: Isaura
authors.initials: I
authors.lastname: Meza
mesh_terms: D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D004317:Doxorubicin / Q000627:therapeutic use*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics*; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D060888:Real-Time Polymerase Chain Reaction; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D051034:Inhibitor of Apoptosis Proteins; D053583:Interleukin-1beta; D004317:Doxorubicin; C494832:BIRC3 protein, human; D000075747:Baculoviral IAP Repeat-Containing 3 Protein; D044767:Ubiquitin-Protein Ligases
keywords: Cell survival genes; Drug sensitivity; IL-1β stimulation