title: Bik subcellular localization in response to oxidative stress induced by chemotherapy, in Two different breast cancer cell lines and a Non-tumorigenic epithelial cell line.
abstract: Cancer chemotherapy remains one of the preferred therapeutic modalities against malignancies despite its damaging side effects. An expected outcome while utilizing chemotherapy is apoptosis induction. This is mainly regulated by a group of proteins known as the Bcl-2 family, usually found within the endoplasmic reticulum or the mitochondria. Recently, these proteins have been located in other sites and non-canonic functions have been unraveled. Bik is a pro-apoptotic protein, which becomes deregulated in cancer, and as apoptosis is associated with oxidative stress generation, our objective was to determine the subcellular localization of Bik either after a direct oxidative insult due to H2 O2 , or indirectly by cisplatin, an antineoplastic agent. Experiments were performed in two human transformed mammary gland cell lines MDA-MB-231 and MCF-7, and one non-tumorigenic epithelial cell line MCF-10A. Our results showed that in MCF-7, Bik is localized within the cytosol and that after oxidative stress treatment it translocates into the nucleus. However, in MDA-MB-231, Bik localizes in the nucleus and translocates to the cytosol. In MCF10A Bik did not change its cellular site after either treatment. Interestingly, MCF10A were more resistant to cisplatin than transformed cell lines. This is the first report showing that Bik is located in different cellular compartments depending on the cancer stage, and it has the ability to change its subcellular localization in response to oxidative stress. This is associated with increased sensitivity when exposed to toxic agents, thus rendering novel opportunities to study new therapeutic targets allowing the development of more active and less harmful agents.
authors.affiliation: Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, México, D.F., México.|Unidad Médica en Genética Humana, Centro Médico Nacional Siglo XXI, México, D.F., Mexico.|Posgrado en Biologia Experimental.
authors.forename: Aglaé
authors.initials: A
authors.lastname: Trejo-Vargas
authors.affiliation: Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, México, D.F., México.|Unidad Médica en Genética Humana, Centro Médico Nacional Siglo XXI, México, D.F., Mexico.
authors.forename: Elisa
authors.initials: E
authors.lastname: Hernández-Mercado
authors.affiliation: Unidad Médica en Genética Humana, Centro Médico Nacional Siglo XXI, México, D.F., Mexico.
authors.forename: Rosa María
authors.initials: RM
authors.lastname: Ordóñez-Razo
authors.affiliation: Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, México, D.F., México.
authors.forename: Roberto
authors.initials: R
authors.lastname: Lazzarini
authors.affiliation: Unidad Médica en Genética Humana, Centro Médico Nacional Siglo XXI, México, D.F., Mexico.
authors.forename: Diego Julio
authors.initials: DJ
authors.lastname: Arenas-Aranda
authors.affiliation: Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, México, D.F., México.
authors.forename: María Concepción
authors.initials: MC
authors.lastname: Gutiérrez-Ruiz
authors.affiliation: Departamento de Ciencias de la Salud, DCBS, Universidad Autónoma Metropolitana Iztapalapa, México, D.F., México.
authors.forename: Mina
authors.initials: M
authors.lastname: Königsberg
authors.affiliation: Instituto Nacional de Geriatria, SSA, Posgrado en Biologia Experimental, UAMI, México, D.F., Mexico.
authors.forename: Armando
authors.initials: A
authors.lastname: Luna-López
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D024101:Mitochondrial Proteins; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D006861:Hydrogen Peroxide; D002945:Cisplatin
keywords: Bik; H2O2; MCF-7; MCF10A; MDA-MB-23; cisplatin; oxidative stress