Format

Send to

Choose Destination
J Zhejiang Univ Sci B. 2019 May;20(5):381-390. doi: 10.1631/jzus.B1900163.

Estrogen receptor coactivator Mediator Subunit 1 (MED1) as a tissue-specific therapeutic target in breast cancer.

Author information

1
Department of Cancer Biology, University of Cincinnati College of Medicine, 3125 Eden Avenue, Cincinnati, OH 45267, USA.

Abstract

Breast cancer, one of the most frequent cancer types, is a leading cause of death in women worldwide. Estrogen receptor (ER) α is a nuclear hormone receptor that plays key roles in mammary gland development and breast cancer. About 75% of breast cancer cases are diagnosed as ER-positive; however, nearly half of these cancers are either intrinsically or inherently resistant to the current anti-estrogen therapies. Recent studies have identified an ER coactivator, Mediator Subunit 1 (MED1), as a unique, tissue-specific cofactor that mediates breast cancer metastasis and treatment resistance. MED1 is overexpressed in over 50% of human breast cancer cases and co-amplifies with another important breast cancer gene, receptor tyrosine kinase HER2. Clinically, MED1 expression highly correlates with poor disease-free survival of breast cancer patients, and recent studies have reported an increased frequency of MED1 mutations in the circulating tumor cells of patients after treatment. In this review, we discuss the biochemical characterization of MED1 and its associated MED1/Mediator complex, its crosstalk with HER2 in anti-estrogen resistance, breast cancer stem cell formation, and metastasis both in vitro and in vivo. Furthermore, we elaborate on the current advancements in targeting MED1 using state-of-the-art RNA nanotechnology and discuss the future perspectives as well.

KEYWORDS:

Mediator Subunit 1 (MED1); Mediator; Estrogen receptor; Breast cancer; Endocrine resistance; RNA nanotechnology

PMID:
31090264
DOI:
10.1631/jzus.B1900163

Supplemental Content

Full text links

Icon for Zhejiang University Press
Loading ...
Support Center