Oncotarget

Research Papers:

Lin28A activates androgen receptor via regulation of c-myc and promotes malignancy of ER−/Her2+ breast cancer

Honghong Shen, Lin Zhao, Xiaolong Feng, Cong Xu, Congying Li and Yun Niu _

PDF  |  HTML  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:60407-60418. https://doi.org/10.18632/oncotarget.11004

Metrics: PDF 1305 views  |   HTML 1634 views  |   ?  


Abstract

Honghong Shen1, Lin Zhao1, Xiaolong Feng1, Cong Xu1, Congying Li1, Yun Niu1

1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Key Laboratory of Breast Cancer Prevention and Therapy, Tianjin Medical University, Ministry of Education, Ti Yuan Bei, Tianjin 300060, People’s Republic of China

Correspondence to:

Yun Niu, email: yunniu2015@126.com

Keywords: breast cancer, Lin28A, androgen receptor, c-myc, Her2

Received: May 17, 2016     Accepted: July 19, 2016     Published: August 2, 2016

ABSTRACT

Having previously demonstrated the co-expression status of the Lin28A and androgen receptor (AR) in ER−/Her2+ breast cancer, we tested the hypothesis that Lin28A can activate AR and promotes growth of ER−/Her2+ breast cancer. The expression of Lin28A and AR were examined after Lin28A siRNA and Lin28A plasmid were transfected into ER−/Her2+ breast cancer cells. Chromatin immune-precipitation (ChIP) analysis and Luciferase Assays were used to evaluate the effect of Lin28A and c-myc on AR promoter activity. MTT assays, Boyden chamber invasion assays, colony formation assays and flow cytometry analysis were performed. ER−/Her2+ breast cancer cells which transfected with Lin28A siRNAs and Lin28A plasmid were injected into nude mice, and tumorigenesis was monitored. Our data showed that Lin28A can induced AR expression in ER−/Her2+ breast cancer cells. ChIP analysis showed that Lin28A stimulates the recruitment of c-Myc to the promoter of the AR gene. Lin28A enhanced growth ability, colonies ability, cells proliferation activities, invasive ability and inhibited cells apoptosis of ER−/Her2+ breast cancer cells. Lin28A high expression cells exhibited significantly higher tumorigenic ability in vivo. Our study demonstrates that Lin28A can activates androgen receptor via regulation of c-myc and promotes malignancy of ER−/Her2+ breast cancer. Our findings underline a novel role for Lin28A in breast cancer development and activation of the AR axis.


Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 11004