Open Collections

UBC Faculty Research and Publications

KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells Li, Juan; Zhang, Baotong; Liu, Mingcheng; Fu, Xing; Ci, Xinpei; A, Jun; Fu, Changying; Dong, Ge; Wu, Rui; Zhang, Zhiqian; Fu, Liya; Dong, Jin-Tang

Abstract

Androgen/androgen receptor (AR) signaling drives both the normal prostate development and prostatic carcinogenesis, and patients with advanced prostate cancer often develop resistance to androgen deprivation therapy. The transcription factor Krüppel-like factor 5 (KLF5) also regulates both normal and cancerous development of the prostate. In this study, we tested whether and how KLF5 plays a role in the function of AR signaling in prostate cancer cells. We found that KLF5 is upregulated by androgen depending on AR in LNCaP and C4-2B cells. Silencing KLF5, in turn, reduced AR transcriptional activity and inhibited androgen-induced cell proliferation and tumor growth in vitro and in vivo. Mechanistically, KLF5 occupied the promoter of AR, and silencing KLF5 repressed AR transcription. In addition, KLF5 and AR physically interacted with each other to regulate the expression of multiple genes (e.g., MYC, CCND1 and PSA) to promote cell proliferation. These findings indicate that, while transcriptionally upregulated by AR signaling, KLF5 also regulates the expression and transcriptional activity of AR in androgen-sensitive prostate cancer cells. The KLF5-AR interaction could provide a therapeutic opportunity for the treatment of prostate cancer.

Item Metadata

Title
KLF5 Is Crucial for Androgen-AR Signaling to Transactivate Genes and Promote Cell Proliferation in Prostate Cancer Cells
Creator
Li, Juan; Zhang, Baotong; Liu, Mingcheng; Fu, Xing; Ci, Xinpei; A, Jun; Fu, Changying; Dong, Ge; Wu, Rui; Zhang, Zhiqian; Fu, Liya; Dong, Jin-Tang
Contributor
Vancouver Prostate Centre
Publisher
Multidisciplinary Digital Publishing Institute
Date Issued
2020-03-21
Description
Androgen/androgen receptor (AR) signaling drives both the normal prostate development and prostatic carcinogenesis, and patients with advanced prostate cancer often develop resistance to androgen deprivation therapy. The transcription factor Krüppel-like factor 5 (KLF5) also regulates both normal and cancerous development of the prostate. In this study, we tested whether and how KLF5 plays a role in the function of AR signaling in prostate cancer cells. We found that KLF5 is upregulated by androgen depending on AR in LNCaP and C4-2B cells. Silencing KLF5, in turn, reduced AR transcriptional activity and inhibited androgen-induced cell proliferation and tumor growth in vitro and in vivo. Mechanistically, KLF5 occupied the promoter of AR, and silencing KLF5 repressed AR transcription. In addition, KLF5 and AR physically interacted with each other to regulate the expression of multiple genes (e.g., MYC, CCND1 and PSA) to promote cell proliferation. These findings indicate that, while transcriptionally upregulated by AR signaling, KLF5 also regulates the expression and transcriptional activity of AR in androgen-sensitive prostate cancer cells. The KLF5-AR interaction could provide a therapeutic opportunity for the treatment of prostate cancer.
Subject
KLF5; androgen receptor; cell proliferation; tumorigenesis; prostate cancer
Genre
Article
Type
Text
Language
eng
Date Available
2020-03-27
Provider
Vancouver : University of British Columbia Library
Rights
CC BY 4.0
DOI
10.14288/1.0389656
URI
http://hdl.handle.net/2429/73821
Affiliation
Medicine, Faculty of; Other UBC; Non UBC; Urologic Sciences, Department of
Citation
Cancers 12 (3): 748 (2020)
Publisher DOI
10.3390/cancers12030748
Peer Review Status
Reviewed
Scholarly Level
Faculty
Rights URI
https://creativecommons.org/licenses/by/4.0/
Aggregated Source Repository
DSpace

Item Media

Item Citations and Data

Rights

CC BY 4.0