TY - JOUR
T1 - DUOX1 silencing in mammary cell alters the response to genotoxic stress
AU - Fortunato, Rodrigo S.
AU - Gomes, Luciana R.
AU - Munford, Veridiana
AU - Pessoa, Carolina Fittipaldi
AU - Quinet, Annabel
AU - Hecht, Fabio
AU - Kajitani, Gustavo S.
AU - Milito, Cristiane Bedran
AU - Carvalho, Denise P.
AU - Menck, Carlos Frederico Martins
N1 - Publisher Copyright:
Copyright © 2018 Rodrigo S. Fortunato et al.
PY - 2018
Y1 - 2018
N2 - DUOX1 is an H2O2-generating enzyme related to a wide range of biological features, such as hormone synthesis, host defense, cellular proliferation, and fertilization. DUOX1 is frequently downregulated in lung and liver cancers, suggesting a tumor suppressor role for this enzyme. Here, we show that DUOX1 expression is decreased in breast cancer cell lines and also in breast cancers when compared to the nontumor counterpart. In order to address the role of DUOX1 in breast cells, we stably knocked down the expression of DUOX1 in nontumor mammary cells (MCF12A) with shRNA. This led to higher cell proliferation rates and decreased migration and adhesion properties, which are typical features for transformed cells. After genotoxic stress induced by doxorubicin, DUOX1-silenced cells showed reduced IL-6 and IL-8 secretion and increased apoptosis levels. Furthermore, the cell proliferation rate was higher in DUOX1-silenced cells after doxorubicin medication in comparison to control cells. In conclusion, we demonstrate here that DUOX1 is silenced in breast cancer, which seems to be involved in breast carcinogenesis.
AB - DUOX1 is an H2O2-generating enzyme related to a wide range of biological features, such as hormone synthesis, host defense, cellular proliferation, and fertilization. DUOX1 is frequently downregulated in lung and liver cancers, suggesting a tumor suppressor role for this enzyme. Here, we show that DUOX1 expression is decreased in breast cancer cell lines and also in breast cancers when compared to the nontumor counterpart. In order to address the role of DUOX1 in breast cells, we stably knocked down the expression of DUOX1 in nontumor mammary cells (MCF12A) with shRNA. This led to higher cell proliferation rates and decreased migration and adhesion properties, which are typical features for transformed cells. After genotoxic stress induced by doxorubicin, DUOX1-silenced cells showed reduced IL-6 and IL-8 secretion and increased apoptosis levels. Furthermore, the cell proliferation rate was higher in DUOX1-silenced cells after doxorubicin medication in comparison to control cells. In conclusion, we demonstrate here that DUOX1 is silenced in breast cancer, which seems to be involved in breast carcinogenesis.
UR - http://www.scopus.com/inward/record.url?scp=85055074578&partnerID=8YFLogxK
U2 - 10.1155/2018/3570526
DO - 10.1155/2018/3570526
M3 - Article
C2 - 29849884
AN - SCOPUS:85055074578
SN - 1942-0900
VL - 2018
JO - Oxidative Medicine and Cellular Longevity
JF - Oxidative Medicine and Cellular Longevity
M1 - 3570526
ER -