2. Academic Validation
  3. Endoplasmic reticulum stress inhibits AR expression via the PERK/eIF2α/ATF4 pathway in luminal androgen receptor triple-negative breast cancer and prostate cancer

Endoplasmic reticulum stress inhibits AR expression via the PERK/eIF2α/ATF4 pathway in luminal androgen receptor triple-negative breast cancer and prostate cancer

  • NPJ Breast Cancer. 2022 Jan 10;8(1):2. doi: 10.1038/s41523-021-00370-1.
Xiaoli Li  # 1 2 3,  Duanfang Zhou  # 1 2,  Yongqing Cai 4,  Xiaoping Yu 1 2,  Xiangru Zheng 5,  Bo Chen 1 2,  Wenjun Li 6,  Hongfang Zeng 1 2,  Moustapha Hassan 7,  Ying Zhao 7,  Weiying Zhou 8 9 10
Affiliations

Affiliations

  • 1 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China.
  • 2 Chongqing Key laboratory of Drug Metabolism, Chongqing, 400016, P.R. China.
  • 3 Key laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, 400016, P.R. China.
  • 4 Department of Pharmacy, Army Medical Center of PLA, Chongqing, 400042, P.R. China.
  • 5 Department of Gastrointestinal Surgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, P.R. China.
  • 6 Department of Pharmacy, The Third Affiliated Hospital of Chongqing Medical University (Gener Hospital), Chongqing, 401120, P.R. China.
  • 7 Experimental Cancer Medicine, Division of Bio-molecular and Cellular Medicine (BCM), Department of Laboratory Medicine, Karolinska Institutet, Huddinge, 141 86, Stockholm, Sweden.
  • 8 Department of Pharmacology, College of Pharmacy, Chongqing Medical University, Chongqing, 400016, P.R. China. wyzhou0118@163.com.
  • 9 Chongqing Key laboratory of Drug Metabolism, Chongqing, 400016, P.R. China. wyzhou0118@163.com.
  • 10 Key laboratory for Biochemistry and Molecular Pharmacology of Chongqing, Chongqing, 400016, P.R. China. wyzhou0118@163.com.
  • # Contributed equally.
PMID: 35013318 DOI: 10.1038/s41523-021-00370-1
Abstract

Androgen Receptor (AR) is an important prognostic marker and therapeutic target in luminal Androgen Receptor triple-negative breast Cancer (LAR TNBC) and prostate Cancer (PCa). Endoplasmic reticulum (ER) stress may activate the unfolded protein response (UPR) to regulate associated protein expression and is closely related to tumor growth and drug resistance. The effect of ER stress on AR expression and signaling remains unclear. Here, we focused on the regulation and underlying mechanism of AR expression induced by ER stress in LAR TNBC and PCa. Western blotting and quantitative RT-PCR results showed that AR expression was markedly decreased under ER stress induced by thapsigargin and brefeldin A, and this effect was dependent on PERK/eIF2α/ATF4 signaling activation. Chromatin immunoprecipitation-PCR and luciferase reporter gene analysis results showed that ATF4 bound to the AR promoter regions to inhibit its activity. Moreover, ATF4 overexpression inhibited tumor proliferation and AR expression both in vitro and in vivo. Collectively, these results demonstrated that ER stress could decrease AR mRNA and protein levels via PERK/eIF2α/ATF4 signaling in LAR TNBC and PCa. Targeting the UPR may be a treatment strategy for AR-dependent TNBC and PCa.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z