IL-1 beta induced methylation of the estrogen receptor ER alpha gene correlates with EMT and chemoresistance in breast cancer cells
Por:
Jimenez-Gardnno, Aura M., Mendoza-Rodriguez, Monica G., Urrutia-Cabrera, Daniel, Dominguez-Robles, Maria C., Perez-Yepez, Eloy A., Tonatiuh Ayala-Sumuano, Jorge, Meza, Isaura
Publicada:
26 ago 2017
Resumen:
Inflammation has been recently acknowledged as a key participant in the
physiopathology of oncogenesis and tumor progression. The inflammatory
cytokine IL-1 beta has been reported to induce the expression of markers
associated with malignancy in breast cancerous cells through
Epithelial-Mesenchymal Transition (EMT). Aggressive breast cancer tumors
classified as Triple Negative do not respond to hormonal treatment
because they lack three crucial receptors, one of which is the estrogen
receptor alpha (ER alpha). Expression of ER alpha is then considered a
good prognostic marker for tamoxifen treatment of this type of cancer,
as the binding of this drug to the receptor blocks the transcriptional
activity of the latter. Although it has been suggested that inflammatory
cytokines in the tumor micro environment could regulate ER alpha
expression, the mechanism(s) involved in this process have not yet been
established. We show here that, in a cell model of breast cancer cells
(6D cells), in which the inflammatory cytokine IL-1 beta induces EMT by
activation of the IL-1 beta/1L-1RI/beta-catenin pathway, the up
regulation of TWIST1 leads to methylation of the ESR1 gene promoter.
This epigenetic modification produced significant decrease of the ER
alpha receptor levels and increased resistance to tamoxifen. The direct
participation of IL-1 beta in these processes was validated by blockage
of the cytokine-induced signaling pathway by wortmannin inactivation of
the effectors PI3K/AKT. These results support our previous reports that
have suggested direct participation of the inflammatory cytokine IL-1
beta in the transition to malignancy of breast cancer cells. (C)
Elsevier Inc. All rights reserved.
Filiaciones:
Jimenez-Gardnno, Aura M.:
Inst Politecn Nacl, Ctr Invest Estudios Avanzados, Dept Biomed Mol, Avenida Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
Mendoza-Rodriguez, Monica G.:
Inst Politecn Nacl, Ctr Invest Estudios Avanzados, Dept Biomed Mol, Avenida Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
Univ Politecn Huatusco, Huatusco 94100, Veracruz, Mexico
Urrutia-Cabrera, Daniel:
Inst Politecn Nacl, Ctr Invest Estudios Avanzados, Dept Biomed Mol, Avenida Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
Dominguez-Robles, Maria C.:
Inst Politecn Nacl, Ctr Invest Estudios Avanzados, Dept Biomed Mol, Avenida Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
Perez-Yepez, Eloy A.:
Univ Nacl Autonoma Mexico, Fac Estudios Super, Unidad Biomed, Tlalnepantla 54090, Mexico
Tonatiuh Ayala-Sumuano, Jorge:
Univ Politecn Huatusco, Huatusco 94100, Veracruz, Mexico
Meza, Isaura:
Inst Politecn Nacl, Ctr Invest Estudios Avanzados, Dept Biomed Mol, Avenida Inst Politecn Nacl 2508, Mexico City 07360, DF, Mexico
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