期刊
ENDOCRINE-RELATED CANCER
卷 29, 期 12, 页码 717-733出版社
BIOSCIENTIFICA LTD
DOI: 10.1530/ERC-22-0108
关键词
prostate epithelium; prostate cancer; androgen receptor; androgen response; cell models
资金
- Academy of Finland
- Sigrid Juselius Foundation [317871, 334774, 312043, 317755]
- Cancer Foundation Finland
- Competitive State Research Financing of the Expert Responsibility area of Tampere University Hospital
- Finnish Cultural Foundation
- Tampere University
- Faculty of Medicine and Health Technology
Development of a cell line model mimicking luminal prostate epithelial cells by modifying the immortalized prostate epithelial cell line RWPE-1 to constitutively express the androgen receptor provides a valuable tool for studying the transformation of the prostate epithelium.
Prostate cancer research suffers from the lack of suitable models to study the role of normal cells in prostate carcinogenesis. To address this challenge, we developed a cell line model mimicking luminal prostate epithelial cells by modifying the immortalized prostate epithelial cell line RWPE-1 to constitutively express the androgen receptor (AR). RWPE-1-AR cells express known AR target genes, and exhibit coexpression of luminal and basal markers characteristic of transient amplifying cells, and an RNA signature resembling prostate luminal progenitor cells. Under unstimulated conditions, constitutive AR expression does not have a biologically significant effect on the proliferation of RWPE-1 cells, but when stimulated by androgens, growth is retarded. The transcriptional response of RWPE-1-AR cells to androgen stimulation involves suppression of the growth-related KRAS pathway and is thus markedly different from that of the prostate cancer cell line LNCaP and its derivative AR-overexpressing LNCaP-ARhi cells, in which growth- and cancer-related pathways are upregulated. Hence, the nonmalignant AR-positive RWPE-1-AR cell line model could be used to study the transformation of the prostate epithelium.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据