Alteration of Y-box binding protein-1 expression modifies the response to endocrine therapy in estrogen receptor-positive breast cancer View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2011-08-24

AUTHORS

Tokiko Ito, Shinobu Kamijo, Hiroto Izumi, Kimitoshi Kohno, Jun Amano, Ken-ichi Ito

ABSTRACT

Y-box binding protein-1 (YB-1) plays an important role in tumor progression and drug resistance. This study examined whether YB-1 is involved in the alteration of response to endocrine therapy in estrogen receptor (ER)-positive breast cancer cells. MCF7 cells that stably expressed YB-1 (MCF7-YB-1) and vector control cells (MCF7-vector) were established. These cells were used to analyze the expression of the factors related to ER and growth factor receptor signaling pathways and responses to antiestrogens (tamoxifen and fulvestrant) and estrogen responsive element (ERE) activity. The effect of knocking down endogenous YB-1 expression was tested in wild-type MCF7 cells. In addition, the expression of YB-1 and the factors related to ER and growth factor receptor signaling pathways were evaluated in clinical breast cancers treated with preoperative chemotherapy. The expression of HER2, AIB1, p-Erk, and c-Myc was increased in MCF7-YB-1 cells. In contrast, knocking down of YB-1 decreased the expression of these factors but increased the expression of ERα in wild-type MCF7 cells. Furthermore, sensitivity to antiestrogens was decreased in the MCF7-YB-1 in comparison to that in MCF7-vector cells. The introduction of YB-1 into MCF7 cells inhibited apoptosis and cell cycle arrest at G1 phase induced by antiestrogens. In MCF7-YB-1 cells, the expression levels of p-Erk and c-Myc were continuously upregulated when cells were treated with either tamoxifen or fulvestrant. The ERE activity was reduced in MCF7-YB-1 cells in comparison to MCF7-vector cells, and the ERE activity in MCF7-YB-1 cells was inhibited by fulvestrant at a lower concentration than that which inhibited the ERE activity in MCF7-vector cells. In ER-positive clinical breast cancers treated with preoperative chemotherapy, significantly more number of specimens that showed increased or positive YB-1 expression after chemotherapy was positive for HER2 expression. These data suggest that alteration of YB-1 may modify the crosstalk between the ER pathway and HER2 pathway in ER-positive breast cancer cells, and consequently, may alter the response to endocrine therapy in ER-positive breast cancer cells. More... »

PAGES

145-159

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s10549-011-1731-8

DOI

http://dx.doi.org/10.1007/s10549-011-1731-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1049867373

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/21863258


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67 c-Myc
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84 estrogen receptor
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86 expression
87 expression levels
88 expression of ERα
89 expression of HER2
90 factor receptor
91 factors
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95 levels
96 low concentrations
97 more number
98 number
99 p-ERK
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103 preoperative chemotherapy
104 progression
105 protein 1
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107 receptor-positive breast cancer
108 receptors
109 resistance
110 response
111 role
112 sensitivity
113 signaling pathways
114 specimens
115 study
116 tamoxifen
117 therapy
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