Knockdown of Chloride Channel-3 Inhibits Breast Cancer Growth In Vitro and In Vivo / 한국유방암학회지
Journal of Breast Cancer
;
: 103-111, 2018.
Article
Dans Anglais
| WPRIM
| ID: wpr-714871
ABSTRACT
PURPOSE:
Chloride channel-3 (ClC-3) is a member of the chloride channel family and plays a critical role in a variety of cellular activities. The aim of the present study is to explore the molecular mechanisms underlying the antitumor effect of silencing ClC-3 in breast cancer.METHODS:
Human breast cancer cell lines MDA-MB-231 and MCF-7 were used in the experiments. Messenger RNA and protein expression were examined by quantitative real-time polymerase chain reaction and western blot analysis. Cell proliferation was measured by the bromodeoxyuridine method, and the cell cycle was evaluated using fluorescence-activated cell sorting. Protein interaction in cells was analyzed by co-immunoprecipitation. Tumor tissues were stained with hematoxylin-eosin and tumor burden was measured using the Metamorph software.RESULTS:
Breast cancer tissues collected from patients showed an increase in ClC-3 expression. Knockdown of ClC-3 inhibited the secretion of insulin-like growth factor (IGF)-1, cell proliferation, and G1/S transition in breast cancer cells. In the mouse xenograft model of human breast carcinoma, tumor growth was significantly slower in animals injected with ClC-3-deficient cells compared with the growth of normal human breast cancer cells. In addition, silencing of ClC-3 attenuated the expression of proliferating cell nuclear antigen, Ki-67, cyclin D1, and cyclin E, as well as the activation of extracellular signal-regulated protein kinases (ERK) 1/2, both in vitro and in vivo.CONCLUSION:
Together, our data suggest that upregulation of ClC-3 by IGF-1 contributes to cell proliferation and tumor growth in breast cancer, and ClC-3 deficiency suppresses cell proliferation and tumor growth via the IGF/IGF receptor/ERK pathway.
Texte intégral:
Disponible
Indice:
WPRIM (Pacifique occidental)
Sujet Principal:
Protein kinases
/
Techniques in vitro
/
Région mammaire
/
Tumeurs du sein
/
Broxuridine
/
ARN messager
/
Facteur de croissance IGF-I
/
Cycle cellulaire
/
Régulation positive
/
Lignée cellulaire
Type d'étude:
Étude pronostique
Limites du sujet:
Animaux
/
Humains
langue:
Anglais
Texte intégral:
Journal of Breast Cancer
Année:
2018
Type:
Article
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