当前位置： SCI文献检索 > CANCER RESEARCH期刊下所有文献 > Breast Cancer Resistance to Antiestrogens Is Enhanced by Increased ER Degradation and ERBB2 Expression.

Breast Cancer Resistance to Antiestrogens Is Enhanced by Increased ER Degradation and ERBB2 Expression.

Abstract：

:Endocrine therapies effectively improve the outcomes of patients with estrogen receptor (ER)-positive breast cancer. However, the emergence of drug-resistant tumors creates a core clinical challenge. In breast cancer cells rendered resistant to the antiestrogen fulvestrant, we defined causative mechanistic roles for the transcription factor YBX1 and the levels of ER and the ERBB2 receptor. Enforced expression of YBX1 in parental cells conferred resistance against tamoxifen and fulvestrant in vitro and in vivo Furthermore, YBX1 overexpression was associated with decreased and increased levels of ER and ERBB2 expression, respectively. In antiestrogen-resistant cells, increased YBX1 phosphorylation was associated with a 4-fold higher degradation rate of ER. Notably, YBX1 bound the ER, leading to its accelerated proteasomal degradation, and induced the transcriptional activation of ERBB2. In parallel fashion, tamoxifen treatment also augmented YBX1 binding to the ERBB2 promoter to induce increased ERBB2 expression. Together, these findings define a mechanism of drug resistance through which YBX1 contributes to antiestrogen bypass in breast cancer cells. Cancer Res; 77(2); 545-56. ©2016 AACR.

journal_name

Cancer Res

journal_title

Cancer research

authors

Shibata T,Watari K,Izumi H,Kawahara A,Hattori S,Fukumitsu C,Murakami Y,Takahashi R,Toh U,Ito KI,Ohdo S,Tanaka M,Kage M,Kuwano M,Ono M

doi

10.1158/0008-5472.CAN-16-1593

subject

Has Abstract

pub_date

2017-01-15 00:00:00

pages

545-556

issue

2

eissn

0008-5472

issn

1538-7445

pii

0008-5472.CAN-16-1593

journal_volume

77

pub_type

杂志文章

相关文献

CANCER RESEARCH文献大全