The role of MYB proto-oncogene like 2 in tamoxifen resistance in breast cancer

被引：12

作者：

Li, Xia ^{[1
]}

Zhang, Xi ^{[1
]}

Wu, Cong-Cong ^{[1
]}

Li, Ping-Ping ^{[1
]}

Fu, Yi-Mou ^{[1
]}

Xie, Li-Hua ^{[1
]}

Sun, Shuang-Shuang ^{[1
]}

Zhou, Ying-Ying ^{[1
]}

Zhu, Bao-Ling ^{[1
]}

机构：

[1] Wenzhou Med Univ, Affiliated Hosp 2, Dept Chemotherapy & Radiotherapy, Yuying Childrens Hosp, 109 Xueyuan West Rd, Wenzhou 325027, Zhejiang, Peoples R China

来源：

JOURNAL OF MOLECULAR HISTOLOGY | 2021年 / 52卷 / 01期

关键词：

MYBL2; Breast cancer; Tamoxifen resistance; Cell cycle; Apoptosis; Migration; B-MYB; CELL-CYCLE; EXPRESSION; PROLIFERATION; CHOLESTEROL; COMPLEX; TRANSCRIPTION; ACTIVATION; APOPTOSIS; AUTOPHAGY;

D O I：

10.1007/s10735-020-09920-6

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Despite the efficacy of tamoxifen in preventing disease relapse, a large portion of breast cancer patients show intrinsic or acquired resistance to tamoxifen, leading to treatment failure and unfavorable clinical outcome. MYB proto-oncogene like 2 (MYBL2) is a transcription factor implicated in the initiation and progression of various human cancers. However, its role in tamoxifen resistance in breast cancer remained largely unknown. In the present study, by analyzing public transcriptome dataset, we found that MYBL2 is overexpressed in breast cancer and is associated with the poor prognosis of breast cancer patients. By establishing tamoxifen-resistant breast cancer cell lines, we also provided evidence that MYBL2 overexpression contributes to tamoxifen resistance by up-regulating its downstream transcriptional effectors involved in cell proliferation (PLK1, PRC1), survival (BIRC5) and metastasis (HMMR). In contrast, inhibiting those genes via MYBL2 depletion suppresses cancer progression, restores tamoxifen and eventually reduces the risk of disease recurrence. All these findings revealed a critical role of MYBL2 in promoting tamoxifen resistance and exacerbating the progression of breast cancer, which may serve as a novel therapeutic target to overcome drug resistance and improve the prognosis of breast cancer patients.

引用

页码：21 / 30

页数：10

共 40 条

[1] Direct transactivation of the anti-apoptotic gene apolipoprotein J (Clusterin) by B-MYB [J].